Showing papers in "Neuroimmunomodulation in 2016"
TL;DR: It is demonstrated that minocycline can ameliorate ischemia-induced brain damage via inhibiting NLRP3 inflammasome activation.
Abstract: Objective: Minocycline, a tetracycline antibiotic, has shown anti-inflammatory effects in cerebral ischemia and neurodegenerative disease; however, the molecular
62 citations
TL;DR: The results suggest that 1,25(OH)2-dihydroxyvitamin D D 3 may exert anti-inflammatory action by facilitating the M2 polarization of human microglial cells.
Abstract: Objective: To explore the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of vitamin D, on M1/M2 polariz
32 citations
TL;DR: Blood leukocyte TLR2 and TLR7/8 responses are impaired in PD, and the association between a decreased TLR response in periphery and damage of brain in PD must be further investigated.
Abstract: Objectives: Toll-like receptors (TLRs) are expressed in several immune cells including blood monocytes and resident macrophages, such as microglia in the central
26 citations
TL;DR: The results suggest that single measurements of plasma concentrations of inflammation-associated cytokines cannot be used to distinguish disease states, however, measurements made over time may correlate with pathogenesis.
Abstract: Objective: Chronic inflammatory processes contribute to the eventual death of motor neurons and the development of symptoms in both idiopathic Parkinson disease (
24 citations
TL;DR: This study revealed for the first time an increase of MC-nerve association and neuropeptide receptor expression on MCs during AR as well as nerve fibres containing receptors for MCs.
Abstract: Objectives: Mast cells (MCs) and nerves play an important role in allergic rhinitis (AR), but little is known about their crosstalk in AR. The aim of this study was to investigate MC-nerve interaction in the human nasal mucosa during AR. Methods: The association between MCs and nerves, the expression of neuropeptide receptors (neurokinin 1 receptor [NK1R], neurokinin 2 receptor [NK2R], calcitonin gene-related peptide receptor [CGRPR], and MrgX2) on MCs, and protease-activated receptor 2 (PAR2) and tyrosine receptor kinase A (TrkA) on nerve fibres in the human nasal mucosa were investigated with immunofluorescence and real-time PCR. Results: The association between MCs and nerves was found to be significantly increased, although the numbers of MCs and nerve fibres were unchanged during AR. MCs expressing tryptase-chymase (MCtc) were frequently associated with nerve fibres and these contacts increased significantly in AR. Neuropeptide receptors NK1R, NK2R, and CGRPR were firstly found to be largely localised on MCs. The number of MCs expressing NK1R and NK2R, but not CGRPR, was significantly increased in AR. Interestingly, MCtc mostly expressed these neuropeptide receptors. The newly discovered tachykinin receptor MrgX2 was not expressed on nasal MCs, but was expressed on gland cells and increased in AR. Additionally, tachykinergic nerve fibres were found to express PAR2 or TrkA as receptors for MCs. Conclusions: This study revealed for the first time an increase of MC-nerve association and neuropeptide receptor expression on MCs during AR as well as nerve fibres containing receptors for MCs. These results suggest that targeting or controlling airway sensory nerve function as a modulator of MCs may prevent allergic airway inflammation such as AR.
24 citations
TL;DR: It is emphasized that coadministration of melatonin and resveratrol can be beneficial in BCCAO-induced vascular dementia through changes in BDNF expressions.
Abstract: Objectives: This study was intended to investigate whether treatment with resveratrol and melatonin alone or in combination can exert neurorestorative effects in
23 citations
TL;DR: AQP4 mediates the suppressive effect of neuroinflammation on hippocampal neurogenesis via regulation of the astroglial response, and is speculated to mediate the synthesis and release of proinflammatory cytokines in glia and then indirectly regulate adult hippocampal Neurogenesis.
Abstract: Objective Aquaporin-4 (AQP4), a key molecule for water homeostasis in the brain, is associated with adult neurogenesis, but its mechanisms regulating adult neural stem cells (aNSC) remain largely unexplored. Neuroinflammation has a relevant influence on adult neurogenesis, which is a common feature in various neurodegenerative diseases. Considering the possible link between neuroinflammation and AQP4, we speculate that AQP4 may mediate the synthesis and release of proinflammatory cytokines in glia and then indirectly regulate adult hippocampal neurogenesis. Methods Using AQP4 knockout mice, we investigated the effects of AQP4 on hippocampal neurogenesis after lipopolysaccharide (LPS)-induced neuroinflammation. Results We unexpectedly found that AQP4 deficiency attenuated the decrease in aNSC proliferation after systemic LPS exposure, accompanied by inhibition of glial activation and suppression of the production of proinflammatory cytokines in the hippocampus. Meanwhile, in vivo studies demonstrated that LPS-induced activated microglia did not express AQP4, indicating the impossibility of direct regulation of AQP4 to activate microglia. Furthermore, we demonstrated in vitro that AQP4 deficiency inhibited astrocyte activation and reduced the release of proinflammatory cytokines from astrocytes. Conclusion Our data suggest that AQP4 mediates the suppressive effect of neuroinflammation on hippocampal neurogenesis via regulation of the astroglial response.
21 citations
TL;DR: The findings suggest that IL-1β can activate mTOR, followed by activated neurons, which is critical in the pathogenesis of MTLE chronicity, and targeting inflammation modulators in MTLE may provide new pathways for therapy of refractory epilepsy.
Abstract: Objective: Mesial temporal lobe epilepsy (MTLE) is the most common type of refractory epilepsy. It is often associated with hippocampal sclerosis, which is histop
21 citations
TL;DR: CXCL12 seems to be involved in the cellular part of the events that take place in the CNS, and therefore it could be considered as a target in MS therapies, with an emphasis on CXCL 12 serum concentrations and its gene polymorphism at position +801.
Abstract: Both cellular and molecular components of the immune system are among the substantial factors involved in the pathogenesis of multiple sclerosis (MS). Accumulating evidence confirms that chemokines, as the main members of the immune system, play key roles in the regulation of immune responses. Immune system genetic parameters are believed to influence the onset of immune system-related diseases. Regarding the significant role of the CXCR4/CXCL12 axis in cell differentiation and survival and homing of hematopoietic progenitors to the bone marrow and regulation of neuronal progenitor cell migration in the central nervous system (CNS), genetic factors can cause an increased expression of CXCL12 and induce a vigorous immune response against CNS antigens in MS patients. Previous studies have indicated that the expression of CXCL12 could be affected by its polymorphisms at position +801 at the region of the CXCL12 3'A genetic variation. Finally, CXCL12 seems to be involved in the cellular part of the events that take place in the CNS, and therefore it could be considered as a target in MS therapies. Thus, this review was aimed to describe the recent progress in understanding the role of CXCL12 in MS, with an emphasis on CXCL12 serum concentrations and its gene polymorphism at position +801.
20 citations
TL;DR: The findings suggest that, in patients with stable CAD, elevated MLR may be associated with depressive symptoms, with increased neuroendocrine-sympathetic activity (marked by CgA) and inflammatory markers that are pertinent to atherosclerosis initiation and progression.
Abstract: Background: Psychosocial stress and depression have been recognized as major risk factors of coronary artery disease (CAD). Although monocytes are known to be key
18 citations
TL;DR: Findings indicate that the administration of BCG offers neuroprotection in the murine model of JE, and BCG should therefore be further investigated as an adjuvant in the management ofJE.
Abstract: Objective: Japanese encephalitis (JE) is a debilitating disease caused by infection with the JE virus (JEV; family: Flaviviridae), which leaves neurological seque
TL;DR: HBOT may alleviate the inflammatory response after TBI by inhibiting the activation of inflammasome signaling, according to the results of this study.
Abstract: Objective: Neuroinflammation plays an important role in secondary tissue damage after traumatic brain injury (TBI). Recently, the inflammasome-mediated inflammatory pathway has been observed in the inflammatory response of TBI. In this study, we investigated the influence of hyperbaric oxygen therapy (HBOT) on inflammasome activation after TBI. Methods: The experimental mice were randomly divided into 4 groups as follows: sham-operated normobaric air (21% O2 at one absolute atmosphere), HBOT only, TBI + normobaric air and TBI + HBOT. Following the evaluation of motor deficits and brain edema, the expression of inflammasome components and effectors was measured by qRT-PCR and Western blotting. Moreover, alterations in IL-1β, IL-18 and high-mobility group box 1 (HMGB1) were calculated by enzyme-linked immunosorbent assay at each time point after injury. Results: HBOT improved motor score and reduced brain edema. Furthermore, it suppressed protein expression of inflammasome components and reduced the levels of IL-1β and IL-18, accompanied by the reduction of HMGB1 in brain tissues and serum. Conclusion: These results suggest that HBOT may alleviate the inflammatory response after TBI by inhibiting the activation of inflammasome signaling.
TL;DR: Results indicate that the frequency of hair washing affects the hair cortisol concentration, and hair cortisol concentrations in the first 3 cm of hair segments proximal to the scalp corresponded to average hair growth rate based on 1 cm/month.
Abstract: There is a growing interest in hair cortisol concentrations as a valuable biomarker for the assessment of metabolic diseases and chronic psychological stress. Fifty-three volunteers were recruited, and hair segments proximal to the scalp were collected from each individual. A cost-effective ball mill was used for the preparation of hair samples, and ELISA was performed to analyze cortisol concentrations. Results indicate that the frequency of hair washing affects the hair cortisol concentration. The group that washed their hair every day had significantly lower cortisol concentrations than the group that washed it less often. However, no significant differences were detected between cosmetic-treated and nontreated hair samples. The study also shows that hair cortisol concentrations in the first 3 cm of hair segments proximal to the scalp corresponded to average hair growth rate based on 1 cm/month. Thus, hair cortisol concentrations of segments 3 cm proximal to the scalp may represent cumulative stress exposure over the previous 3 months. These findings will allow more widespread research to validate the utility of hair cortisol as a potential biomarker to assess chronic stress.
TL;DR: These subgroups must be taken into account for the clinical follow-up of patients with MS in order to provide them with a better and more personalized treatment, and also for a deep and detailed analysis of progressive disease.
Abstract: Objective: The present study was specifically designed to discern the possible existence of subgroups of patients with the relapsing-remitting form of multiple sc
TL;DR: In addition to IL-6 and IL-17A, IL-16 and CCL19 act as proinflammatory cytokines/chemokines, while IL-19 plays a protective role in NMOSD pathogenesis.
Abstract: Objective: To screen cytokines and chemokines and determine their dynamic changes in the serum and cerebrospinal fluid (CSF) of patients with neuromyelitis optica spectrum disorder (NMOSD). Methods: Eight NMOSD with seropositive aquaporin-4 antibody (AQP4-IgG) were enrolled, as well as 8 matched patients with multiple sclerosis (MS) and 8 with noninflammatory neurological diseases, who were included as controls. In total, 102 cytokines and 34 chemokines were detected in the CSF and serum of NMOSD patients and controls. Results: CSF interleukin (IL)-17A levels were significantly higher in NMOSD patients in the relapsing phase (27.15 ± 11.33) than in those in the remitting phase (10.04 ± 3.11, p = 0.0017), and patients with MS (14.72 ± 3.20, p = 0.0283) and other controls (10.39 ± 11.38, p = 0.0021). CSF IL-6 levels were higher in the NMOSD patients in the relapsing phase (12.23 ± 3.47) than in those in the remitting phase (5.87 ± 2.78, p = 0.0001), and MS patients (7.38 ± 2.35, p = 0.0033) and other controls (7.50 ± 0.37, p = 0.0043). CSF CCL19 levels were also significantly higher in NMOSD patients in the relapsing phase (35.87 ± 27.07) than in those in the remitting phase (10.71 ± 3.62, p = 0.0215). Serum IL-19 levels were lower in NMOSD patients in the relapsing phase (6.23 ± 1.95) than in those in the remitting phase (10.72 ± 4.46, p = 0.0092). Further, there was a positive, significant correlation between serum IL-9 concentration and the Expanded Disability Status Scale score in the NMOSD patients in the relapsing phase ( p = 0.04). Conclusion: In addition to IL-6 and IL-17A, IL-16 and CCL19 act as proinflammatory cytokines/chemokines, while IL-19 plays a protective role in NMOSD pathogenesis.
TL;DR: After stimulation with LPS, NOD mice display an increased microglial proliferation and an exaggerated inflammatory brain response with reduced BDNF and PDGF expression and increased sickness behaviour as compared to controls.
Abstract: The non-obese diabetic (NOD) mouse, an established model for autoimmune diabetes, shows an exaggerated reaction of pancreas macrophages to inflammatory stimuli. NOD mice also display anxiety when immune-stimulated. Chronic mild brain inflammation and a pro-inflammatory microglial activation is critical in psychiatric behaviour. Objective: To explore brain/microglial activation and behaviour in NOD mice at steady state and after systemic lipopolysaccharide (LPS) injection. Methods: Affymetrix analysis on purified microglia of pre-diabetic NOD mice (8-10 weeks) and control mice (C57BL/6 and CD1 mice, the parental non-autoimmune strain) at steady state and after systemic LPS (100 μg/kg) administration. Quantitative PCR was performed on the hypothalamus for immune activation markers (IL-1β, IFNγ and TNFα) and growth factors (BDNF and PDGF). Behavioural profiling of NOD, CD1, BALB/c and C57BL/6 mice at steady state was conducted and sickness behaviour/anxiety in NOD and CD1 mice was monitored before and after LPS injection. Results: Genome analysis revealed cell cycle/cell death and survival aberrancies of NOD microglia, substantiated as higher proliferation on BrdU staining. Inflammation signs were absent. NOD mice had a hyper-reactive response to novel environments with some signs of anxiety. LPS injection induced a higher expression of microglial activation markers, a higher brain pro-inflammatory set point (IFNγ, IDO) and a reduced expression of BDNF and PDGF after immune stimulation in NOD mice. NOD mice displayed exaggerated and prolonged sickness behaviour after LPS administration. Conclusion: After stimulation with LPS, NOD mice display an increased microglial proliferation and an exaggerated inflammatory brain response with reduced BDNF and PDGF expression and increased sickness behaviour as compared to controls.
TL;DR: LA causes a reduction in the severity of locomotor activity, as well as in the activation of NF-κB and the number of proinflammatory markers in rats with EAE, which suggest the use of this agonist as a potential therapeutic approach for multiple sclerosis.
Abstract: Objective: Recent findings have shown that gonadotropin-releasing hormone (GnRH) administration in an animal model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE) improves clinical signs of locomotion. The present study was designed to determine whether the administration of the synthetic analog of GnRH, leuprolide acetate (LA) - besides its effects on clinical signs of locomotion - also has an effect on the activation/expression levels of molecular markers of EAE, namely transcription nuclear factor (NF)-κB and the proinflammatory cytokines IL-1s, IL-17A, IL-23 and TNF-a. Methods: EAE spinal cords were collected from control and LA-administered rats. Lumbar sections were processed at four different time points during the course of the disease to analyze NF-κB activation by chemiluminescent Western blot, and during the EAE recovery phase to evaluate proinflammatory cytokine levels by quantitative real-time PCR. Results: It was found that LA administration to EAE rats promoted a significant reduction of NF-κB activation during the course of the disease and also decreased the mRNA expression levels of the proinflammatory cytokines IL-1s, IL-17A and TNF-a in the EAE recovery phase; both effects are consistent with the decrease in the severity of clinical signs of locomotion induced by the treatment. Conclusion: LA causes a reduction in the severity of locomotor activity, as well as in the activation of NF-κB and the number of proinflammatory markers in rats with EAE. These results suggest the use of this agonist as a potential therapeutic approach for multiple sclerosis.
TL;DR: It is proved that animals with TLR4 deficiency have higher protection against ischemia and that the absence ofTLR4 reduces neuroinflammation and injuries associated with brain trauma, and that TLR 4 deficiency may play a neuroprotective role in the occurrence of stroke.
Abstract: Stroke is a prevalent and dangerous health problem, which triggers an intense inflammatory response to Toll-like receptor (TLR) activation. TLRs are the essential components of the response of the innate immunity system, and, therefore, they are one of the key factors involved in recognizing pathogens and internal ligands. Among TLRs, TLR4 significantly participates in the induction of inflammation and brain functions; hence, it has been hypothesized that this molecule is associated with several immune-related brain diseases such as stroke. It has also been proved that animals with TLR4 deficiency have higher protection against ischemia and that the absence of TLR4 reduces neuroinflammation and injuries associated with brain trauma. TLR4 deficiency may play a neuroprotective role in the occurrence of stroke. This article reviews recent information regarding the impact of TLR4 on the pathogenicity of stroke.
TL;DR: The parasite-derived secretion product Av-cystatin inhibits proinflammatory mechanisms of LPS-induced microglia with IL-10, a potential key mediator.
Abstract: Objective: The aim of this study was to examine whether the natural protease inhibitor Av-cystatin (rAv17) of the parasitic nematode Acanthocheilonema vi
TL;DR: Data suggest an anti-inflammatory role for biogenic amines in MS, and patients with relapsing-remitting MS were examined, which is presumably autoimmune disease of the central nervous system.
Abstract: Objective: Multiple sclerosis (MS) is a demyelinating, presumably autoimmune disease of the central nervous system. Biogenic amines may participate in MS pathogenesis modulating immune cell activity and cytokine production. Methods: Forty-three patients with relapsing-remitting MS were examined. Serotonin (SE), norepinephrine (NE) and epinephrine (EPI) concentrations in sera were measured by ELISA. The functional activity of Th17 and Th1 cells was assessed by the ability of peripheral blood mononuclear cells (PBMCs) to produce interferon-gamma (IFN-γ) and interleukin-17 (IL-17) and cell proliferation upon stimulation with microbeads coated with anti-CD3 and anti-CD28 antibodies. To evaluate the effect of biogenic amines on Th17 and Th1 cells, PBMCs were cultured in the presence of SE and NE. Statistical analysis was performed using Prism 6 software. Results: Concentrations of SE and EPI in sera were not different between the groups. Concentrations of NE in sera from MS patients were lower than those in the healthy control group. The production of IL-17 and IFN-γ in MS patients in relapse was higher than that in patients in remission or in the control group. SE at a concentration of 10-4M suppressed IL-17 production. NE at a concentration of 10-4M suppressed both IL-17 and IFN-γ production. Conclusions: These data suggest an anti-inflammatory role for biogenic amines in MS.
TL;DR: Melatonin adsorbed to polyethylene glycol (PEG) microspheres exerts antitumor effects on human MCF-7 breast cancer cells, and clinical tests must be performed to confirm the use of melatonin adsorsed to PEGmicrospheres as an alternative therapy against cancer.
Abstract: Although melatonin exhibits oncostatic properties such as antiproliferative effects, the oral bioavailability of this hormone is less than 20%. Modified drug release systems have been used to improve the pharmacological efficiency of drugs. These systems can change the pharmacokinetics and biodistribution of the associated drugs. Thus, this study investigated the effect of melatonin adsorbed to polyethylene glycol (PEG) microspheres on MCF-7 human breast cancer cells. The MCF-7 cells were obtained from the American Type Culture Collection. MCF-7 cells were preincubated for 24 h with or without melatonin (100 ng/ml), PEG microspheres or melatonin adsorbed to PEG microspheres (100 ng/ml). Viability, intracellular calcium release and apoptosis in MCF-7 cells were determined by flow cytometry. MCF-7 cells incubated with melatonin adsorbed to PEG microspheres showed a lower viability rate (40.0 ± 8.3 with melatonin adsorbed to PEG microspheres compared to 54.1 ± 7.3 with melatonin; 81.8 ± 12.5 with PEG microsphere and 92.7 ± 4.1 with medium), increased spontaneous intracellular Ca2+ release (27.0 ± 8.6 with melatonin adsorbed to PEG microspheres compared to 21.5 ± 13.4 with melatonin; 10.1 ± 5.4 with PEG microsphere and 9.1 ± 5.6 with medium) and increased apoptosis index (51.2 ± 2.7 with melatonin adsorbed to PEG microspheres compared to 36.0 ± 2.1 with melatonin; 4.9 ± 0.5 with PEG microsphere and 3.1 ± 0.6 with medium). The results indicate that melatonin adsorbed to PEG microspheres exerts antitumor effects on human MCF-7 breast cancer cells. However, clinical tests must be performed to confirm the use of melatonin adsorbed to PEG microspheres as an alternative therapy against cancer.
TL;DR: Rutin improves neurological outcome by protecting neural cells against apoptosis via mechanisms that involve the mitochondria following TBI, using the weight-drop model of traumatic brain injury in male mice.
Abstract: Rutin reportedly conveys many beneficial effects, including neuroprotection in brain injury. However, the mechanisms underlying these effects are still not well understood. This study investigates the effect of rutin on potential mechanisms for neuroprotective effects, using the weight-drop model of traumatic brain injury (TBI) in male mice treated either with rutin or a vehicle via intraperitoneal injection 30 min after TBI. After euthanasia and 24 h after TBI, all mice were examined by tests, including neurologic scores, blood-brain barrier permeability, brain water content and neuronal cell death in the cerebral cortex. Results indicate that the levels of cytochrome c, malondialdehyde (MDA) and superoxide dismutase (SOD) were restored by rutin treatment. Rutin treatment resulted in the downregulation of caspase-3 expression in a reduced number of positive cells under terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, and also the improved survival of neurons. Furthermore, pretreatment levels of MDA were restored, while Bcl-2-associated X protein translocation to mitochondria and cytochrome c release into cytosol were reduced by rutin treatment. Our results demonstrate that rutin improves neurological outcome by protecting neural cells against apoptosis via mechanisms that involve the mitochondria following TBI.
TL;DR: In this paper, the activation of STAT1 is directly downstream of the cytokine receptors that signal from specific proinflammatory cytokines known to be dysregulated in the human body, and it is shown that STAT1 activation is downstream of cytokine receptor activation.
Abstract: Objective: Activation of STAT1 is directly downstream of the cytokine receptors that signal from specific proinflammatory cytokines known to be dysregulated in sc
TL;DR: Adipokines may be involved in the psychiatric features observed in FXS patients, and the role of adiponectin and leptin in the pathophysiology of FXS is hypothesized.
Abstract: Fragile X syndrome (FXS) is the most common form of familial mental retardation and one of the leading known causes of autism. The mutation responsible for FXS is a large expansion of the CGG repeats
TL;DR: A cell-based high-throughput screen to identify small molecule inhibitors for NMO-IgG and AQP4 binding is developed, and suggests a potential therapeutic value of isotetrandrine in NMO.
Abstract: Objective: Neuromyelitis optica (NMO) is a severe neurological demyelinating autoimmune disease that affects the optic nerves and spinal cord with no cure and no
TL;DR: It is found that NaHS significantly increased the latency and decreased the duration of hyperthermic seizures and NaHS-treated pups showed less impairment in learning and memory.
Abstract: Objective: Hydrogen sulfide (H2S), as a novel gasotransmitter, plays important roles in a number of physiological and pathological processes. Its effectiveness has been demonstrated in different types of brain disorders but not in repetitive febrile seizure (febrile status epilepticus; FSE) models. This study aims to test whether a donor of H2S sodium sulfhydrate (NaHS) is also effective for FSE in rats. Methods: FSE was induced in rat pups on postnatal day 10 in water at 45.0 ± 0.1°C for 10 consecutive days with or without preadministration of NaHS. Following evaluation of the latency and duration of hyperthermic seizures, impairment in learning and memory was measured by the Morris water maze test. Moreover, alterations of the microglial response and the production of proinflammatory cytokines IL-1β and TNF-α were calculated in the hippocampus. Results: We found that NaHS significantly increased the latency and decreased the duration of hyperthermic seizures. Furthermore, NaHS-treated pups showed less impairment in learning and memory. In addition, NaHS inhibited FSE-induced microglial responses and suppressed the production of IL-1β and TNF-α in the hippocampus. Conclusion: NaHS appears to be effective for the treatment of FSE in infants and children, in part due to its anti-inflammatory action.
TL;DR: Data show that TLR3 signaling contributes to Wallerian degeneration after peripheral nerve injury by affecting Schwann cell activation and macrophage recruitment to injured nerves.
Abstract: Objective: It is well known that Schwann cells play an important role in Wallerian degeneration after peripheral nerve injury. Previously, we reported that toll-like receptor 3 (TLR3) is expressed on Schwann cells, implicating its role in Schwann cell activation during Wallerian degeneration. In this study, we tested this possibility using TLR3 knock-out mice. Methods: Sciatic nerve-crush injury was induced in wild-type and TLR3 knock-out mice. Histological sections of the sciatic nerve were analyzed for Wallerian degeneration on days 3 and 7 after injury. The level of macrophage infiltration was measured by real-time RT-PCR, flow cytometry and immunohistochemistry. The macrophage-recruiting chemokine gene expressions in the injured nerve were determined by real-time RT-PCR. Results: In TLR3 knock-out mice, the nerve injury-induced axonal degeneration and subsequent axonal debris clearance were reduced compared to in wild-type mice. In addition, nerve injury-induced macrophage infiltration into injury sites was attenuated in TLR3 knock-out mice and was accompanied by reduced expression of macrophage-recruiting chemokines such as CC-chemokine ligands (CCL)2/MCP-1, CCL4/MIP-1β and CCL5/RANTES. These macrophage-recruiting chemokines were induced in primary Schwann cells upon TLR3 stimulation. Finally, intraneural injection of polyinosinic-polycytidylic acid, a synthetic TLR3 agonist, induced macrophage infiltration into the sciatic nerve in vivo. Conclusion: These data show that TLR3 signaling contributes to Wallerian degeneration after peripheral nerve injury by affecting Schwann cell activation and macrophage recruitment to injured nerves.
TL;DR: Adiponectin may be a resilience biomarker for MD in HCV-infected patients, and higher levels of sTNFR1 during IFN treatment were associated with sustained virological response.
Abstract: Objective: Major depression (MD) is a condition associated with both hepatitis C virus (HCV) infection and pegylated interferon (IFN)-α treatment. IFN induces a d
TL;DR: This study showed that the abnormalities in specific subsets of CD4+ T cells are associated with sympathetic hyperactivity in ACS patients, and may provide surprising insights into the pathogenesis of arteriosclerosis, involving the regulation of the sympathetic nervous system on immune inflammation.
Abstract: Objective: To observe the effects of sympathetic overactivity on the immune system involved in the imbalance of T helper (Th) lymphocytes, we investigated the correlation between autonomic dysregulation and the generation of regulatory T (Treg) and Th1 chemokines in patients with acute coronary syndrome (ACS). Methods: Blood samples obtained from patients with coronary artery disease and controls were analyzed for levels of Th1 and Treg cells and their associated cytokines by flow cytometry. In addition, the activity of the cyclic adenosine monophosphate (cAMP), the levels of norepinephrine (NE), epinephrine (EPI) and serum cytokines, and the activity of protein kinase A (PKA) were analyzed by Western blot, radioimmunoassay, high-performance liquid chromatography and enzyme-linked immunoassay, respectively. All subjects were evaluated for heart rate variability (HRV). Results: Levels of Th1 cells and T-bet (a T-box transcription factor), NE, EPI, cAMP and PKA significantly increased (all p Conclusions: This study showed that the abnormalities in specific subsets of CD4+ T cells are associated with sympathetic hyperactivity in ACS patients. It may provide surprising insights into the pathogenesis of arteriosclerosis, involving the regulation of the sympathetic nervous system on immune inflammation.
TL;DR: Neuromyelitis optica spectrum disorder is closely associated with elevated autoantibodies, particularly antinuclear and anti-SSA/Ro antibodies and rarely coexists with organ-specific autoimmune diseases.
Abstract: Objective: To investigate the relationship between neuromyelitis optica spectrum disorder (NMOSD) and autoantibodies. Methods: Blood samples of 108 NMOSD patients and 38 controls were collected from January 2012 to August 2014. Immunological parameters, including anti-aquaporin 4, antinuclear, anti-ribonucleoprotein, anti-SM, anti-SSA/Ro, anti-SSB/La and anti-ribosomal P-protein autoantibodies were examined. Results: The NMOSD group exhibited a significantly higher percentage of anti-aquaporin 4 antibodies compared with the control group (76.9 vs. 0.0%, p = 0). The positive rates for antinuclear and anti-SSA antibodies in the NMOSD group were also higher than in the control group (35.2 vs. 11.8%, p = 0.001; 13.0 vs. 0.0%, p = 0.044). In total, 36.1% of the patients in the NMOSD group were seropositive for autoantibodies but only 8.3% were diagnosed with definite systemic autoimmune disorders. Conclusions: NMOSD is closely associated with elevated autoantibodies, particularly antinuclear and anti-SSA/Ro antibodies. NMOSD rarely coexists with organ-specific autoimmune diseases.