Showing papers on "Myeloperoxidase published in 2011"
TL;DR: It is shown that neutrophils from donors who are completely deficient in MPO fail to form neutrophil extracellular traps (NETs), indicating that MPO is required for NET formation.
585 citations
TL;DR: It was shown that RvD1 improved survival rate and attenuated ALI in mice induced by LPS, and the protective mechanisms might be related to selective reaction with ALX, which inhibits MAPKs and NF-κB pathway.
172 citations
TL;DR: Evidence is provided for myeloperoxidase (MPO), an abundant PMN-derived heme protein, facilitating PMN recruitment by its positive surface charge, which highlights a principal mechanism of PMN attraction driven by physical forces.
148 citations
TL;DR: 2-thioxanthines inhibited MPO in plasma and decreased protein chlorination in a mouse model of peritonitis and slowed but did not prevent neutrophils from killing bacteria and were poor inhibitors of thyroid peroxidase.
141 citations
TL;DR: New insights into the pathogenesis of ANCA-associated vasculitides have opened new ways for targeted treatment and microbial factors, derived in particular from S aureus and Gram-negative bacteria, could play a part in disease induction and expression.
Abstract: Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides are characterised by necrotising inflammation of small vessels in conjunction with ANCA directed to either proteinase 3 (PR3) or myeloperoxidase (MPO). The aetiopathogenesis of these disorders is still not fully elucidated but clinical as well as in vitro and in vivo experimental data strongly suggest a role for the autoimmune responses to PR3 and MPO in disease development. Clinically, PR3-ANCA are strongly associated with granulomatous vasculitis as in Wegener's granulomatosis, and MPO-ANCA with necrotising small vessel vasculitis as in microscopic polyangiitis. Levels of PR3-ANCA and MPO-ANCA do, however, not fully reflect disease activity. In vitro, ANCA activate primed neutrophils to release lytic enzymes and reactive oxygen species, a process reinforced by the alternative pathway of complement. In the context of endothelial cells, this process leads to endothelial detachment and lysis. In vivo experimental studies have clearly demonstrated the pathogenic potential of MPO-ANCA for necrotising glomerulonephritis and pulmonary capillaritis. For PR3-ANCA-associated granulomatous vasculitis, an animal model is lacking. Here, effector T cells, in particular Th17 cells, appear to have a major pathogenic role in addition to ANCA. Finally, microbial factors, derived in particular from S aureus and Gram-negative bacteria, could play a part in disease induction and expression. These new insights into the pathogenesis of ANCA-associated vasculitides have opened new ways for targeted treatment.
137 citations
TL;DR: The present results raise the possibility that HDL carbamylation contributes to foam cell formation in atherosclerotic lesions through a pathway requiring the HDL-receptor scavenger receptor class B, type I.
Abstract: Carbamylation of proteins through reactive cyanate has been demonstrated to predict an increased cardiovascular risk. Cyanate is formed in vivo by breakdown of urea and at sites of inflammation by the phagocyte protein myeloperoxidase. Because myeloperoxidase (MPO) associates with high-density lipoprotein (HDL) in human atherosclerotic intima, we examined in the present study whether cyanate specifically targets HDL. Mass spectrometry analysis revealed that protein carbamylation is a major posttranslational modification of HDL. The carbamyllysine content of lesion-derived HDL was more than 20-fold higher in comparison with 3-chlorotyrosine levels, a specific oxidation product of MPO. Notably, the carbamyllysine content of lesion-derived HDL was five- to eightfold higher when compared with lesion-derived low-density lipoprotein (LDL) or total lesion protein and increased with lesion severity. The carbamyllysine content of HDL, but not of LDL, correlated with levels of 3-chlorotyrosine, suggesting ...
136 citations
TL;DR: SB-656933 is a CXCR2 antagonist that demonstrates dose-dependent effects on neutrophil activation and recruitment within a well-tolerated dose range and may be an effective agent in neutrophIL-predominant diseases.
Abstract: WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Receptor antagonists that block the binding of chemokines such as CXCL8 (IL-8) are effective in animals models of neutrophil-mediated inflammation.
• It has been hypothesized that selective inhibition of neutrophil trafficking and activation may be a useful adjunct for the treatment of inflammatory airway diseases such as chronic obstructive pulmonary disease or cystic fibrosis. A CXCR1/2 receptor antagonist has shown activity in an ozone challenge model in humans.
WHAT THIS STUDY ADDS
• SB-656933, a selective CXCR2 antagonist, is safe and well-tolerated at single doses and is shown to inhibit agonist (CXCL1)-mediated expression of the CD11b on peripheral blood neutrophils as well as ozone-induced airway neutrophilia in healthy subjects.
AIMS To determine the safety and tolerability of a novel selective CXCR2 antagonist and assess its pharmacodynamic effects using measures of neutrophil activation and function, including CD11b expression in whole blood and ozone-induced airway inflammation in healthy subjects.
METHODS Flow cytometric determination of ex vivo CXCL1-induced CD11b expression on peripheral blood neutrophils was performed following single dose oral administration of SB-656933 (dose range 2–1100 mg). A subsequent randomized study (placebo, 50 mg and 150 mg) was performed to explore the dose–response for ozone-induced airway inflammation, as measured by sputum biomarkers.
RESULTS Oral administration of SB-656933 resulted in significant inhibition of CXCL1-induced CD11b expression on peripheral blood neutrophils at single doses greater than or equal to 50 mg. Maximum inhibition (70%) relative to placebo was observed following administration of SB-656933 400 mg (95% CI 60%, 77%). This was sustained up to a dose of 1100 mg. Single doses of SB-656933 reduced ozone-induced airway inflammation in a dose-dependent manner. Relative to placebo, there were 55% (95% CI 20%, 75%) and 74% (95% CI 55%, 85%) fewer neutrophils in the sputum of subjects after a single dose of 50 mg or 150 mg, respectively. There was a corresponding reduction in myeloperoxidase concentrations in the sputum supernatant of 32.8% (95% CI 9.2, 50.3) and 50.5% (95% CI 33.3, 63.3). SB-656933 was safe and well-tolerated at all doses.
CONCLUSIONS SB-656933 is a CXCR2 antagonist that demonstrates dose-dependent effects on neutrophil activation and recruitment within a well-tolerated dose range. These data suggest that SB-656933 may be an effective agent in neutrophil-predominant diseases.
131 citations
TL;DR: Results show that neutrophil activation occurring during inflammation and sepsis could be detected by plasma MPO concentration, and these concentrations may be a marker of the neutrophils proliferation and severity of inflammation.
126 citations
TL;DR: It is proposed that urate is a physiological substrate for MPO that is oxidized to the urate radical and the reactions of this radical with superoxide and nitric oxide provide a plausible link between urate and MPO in cardiovascular disease.
114 citations
TL;DR: Results suggest that naringin shows anti-inflammatory effects through inhibiting lung edema, MPO and iNOS activities, TNF-α secretion and pulmonary neutrophil infiltration by blockade of NF-κB in LPS-induced ALI.
112 citations
TL;DR: It is concluded that MPs generated by decompression stresses precipitate neutrophil activation and vascular damage.
Abstract: Progressive elevations in circulating annexin V-coated microparticles (MPs) derived from leukocytes, erythrocytes, platelets, and endothelial cells are found in mice subjected to increasing decompression stresses. Individual MPs exhibit surface markers from multiple cells. MPs expressing platelet surface markers, in particular, interact with circulating neutrophils, causing them to degranulate and leading to further MP production. MPs can be lysed by incubation with polyethylene glycol (PEG) telomere B surfactant, and the number of circulating MPs is reduced by infusion of mice with PEG or antibody to annexin V. Myeloperoxidase deposition and neutrophil sequestration in tissues occur in response to decompression, and the pattern differs among brain, omentum, psoas, and leg skeletal muscle. Both MP abatement strategies reduce decompression-induced intravascular neutrophil activation, neutrophil sequestration, and tissue injury documented as elevations of vascular permeability and activated caspase-3. We conclude that MPs generated by decompression stresses precipitate neutrophil activation and vascular damage.
TL;DR: The facile synthesis and properties of a new boron-dipyrromethene (BODIPY) dye bearing a methylthioether group are reported, and its biological application as a highly sensitive and selective dye is reported.
Abstract: Reactive oxygen species (ROS) are essential for a wide range of biological and pathological events. [1] During infection and inflammation, the phagocytic leukocytes, including neutrophils, monocytes, and macrophages generate reactive oxygen species (ROS) to kill invading bacteria and pathogens. [2] Among ROS, hypochlorous acid (HOCl/OCl )i s a highly reactive oxygen species produced from hydrogen peroxide (H2O2) and chloride ions (Cl ) by the enzyme myeloperoxidase (MPO), which is secreted by activated neutrophils. [3] Although hypochlorous acid plays important roles in the human immune-defense system, overproduction of ROS in living organism has detrimental effects on biological molecules, including nucleic acids, lipids, and proteins, resulting in the inhibition of various protein functions, and contributes to the progression of numerous human diseases, such as atherosclerosis, cancer, cardiovascular diseases, and rheumatoid arthritis. [4] Despite its importance in human health and disease, not as much is known about the mechanism of action and specific roles of HOCl in living systems in comparison with other ROS, owing to slower progress in the development of suitable probes. Several fluorescence probes for the detection and visualization of HOCl in living cells have recently been developed on the basis of the strong oxidizing properties of HOCl. [5–7] HOCl-induced oxidation reactions were employed in the design of fluorescent probes in which the fluorescence properties were regulated by the conversion of the spirocyclic form of rhodamine fluorophores into their ringopened form, [5] or through photoinduced-electron-transfer processes. [6] To facilitate practical applications of such probes, next-generation designs should emphasize higher analyte selectivity, limit susceptibility to autooxidation, and avoid demanding multistep syntheses. Herein, we report the facile synthesis and properties of a new boron-dipyrromethene (BODIPY) dye bearing a methylthioether group, and its biological application as a highly sensitive and selective
TL;DR: It is demonstrated for the first time that IG possessed marked protective effects on experimental colitis through its antioxidation and inhibiting inflammatory mediators by down-regulation of the expressions of NF-κBp65.
TL;DR: H(2) saline has an anti-inflammatory effect on rat hearts with regional myocardial I/R, presenting as significant improvement of heart function parameters 24h after reperfusion.
TL;DR: It is unknown if pro‐ and anti‐inflammatory mediators in acute lung inflammation induced by intestinal ischemia and reperfusion (i‐I/R) can be modulated by low‐level laser therapy (LLLT).
Abstract: Background and Objective
It is unknown if pro- and anti-inflammatory mediators in acute lung inflammation induced by intestinal ischemia and reperfusion (i-I/R) can be modulated by low-level laser therapy (LLLT).
Study Design/Material and Methods
A controlled ex vivo study was developed in which rats were irradiated (660 nm, 30 mW, 0.08 cm2 of spot size) on the skin over the right upper bronchus 1 hour post-mesenteric artery occlusion and euthanized 4 hours later. For pretreatment with anti-tumor necrosis factor (TNF) or IL-10 antibodies, the rats received either one of the agents 15 minutes before the beginning of reperfusion.
Methods
Lung edema was measured by the Evans blue extravasation and pulmonary neutrophils influx was determined by myeloperoxidase (MPO) activity. Both TNF and IL-10 expression and protein in lung were evaluated by RT-PCR and ELISA, respectively.
Results
LLLT reduced the edema (80.1 ± 41.8 µg g−1 dry weight), neutrophils influx (0.83 ± 0.02 × 106 cells ml−1), MPO activity (2.91 ± 0.60), and TNF (153.0 ± 21.0 pg mg−1 tissue) in lung when compared with respective control groups. Surprisingly, the LLLT increased the IL-10 (0.65 ± 0.13) in lung from animals subjected to i-I/R. Moreover, LLLT (0.32 ± 0.07 pg ml−1) reduced the TNF-α level in RPAECs when compared with i-I/R group. The presence of anti-TNF or IL-10 antibodies did not alter the LLLT effect on IL-10 (465.1 ± 21.0 pg mg−1 tissue) or TNF (223.5 ± 21.0 pg mg−1 tissue) in lung from animals submitted to i-I/R.
Conclusion
The results indicate that the LLLT attenuates the i-I/R-induced acute lung inflammation which favor the IL-10 production and reduce TNF generation. Lasers Surg. Med. 43:410–420, 2011. © 2011 Wiley-Liss, Inc.
TL;DR: Findings implicate Btk as an important regulator of neutrophilic granulocyte maturation and function in vivo and in the Arthus reaction, an acute inflammatory response, neutrophil migration into tissues, edema formation, and hemorrhage are significantly reduced in Btk-deficient animals.
TL;DR: It was concluded that there is redundancy in the primary immune response, with eosinophils killing the larvae through an MBP-dependent mechanism and neutrophils Killing the worms through an MPO- dependent mechanism.
Abstract: Eosinophils and neutrophils contribute to larval killing during the primary immune response, and neutrophils are effector cells in the secondary response to Strongyloides stercoralis in mice. The objective of this study was to determine the molecular mechanisms used by eosinophils and neutrophils to control infections with S. stercoralis. Using mice deficient in the eosinophil granule products major basic protein (MBP) and eosinophil peroxidase (EPO), it was determined that eosinophils kill the larvae through an MBP-dependent mechanism in the primary immune response if other effector cells are absent. Infecting PHIL mice, which are eosinophil deficient, with S. stercoralis resulted in development of primary and secondary immune responses that were similar to those of wild-type mice, suggesting that eosinophils are not an absolute requirement for larval killing or development of secondary immunity. Treating PHIL mice with a neutrophil-depleting antibody resulted in a significant impairment in larval killing. Naive and immunized mice with neutrophils deficient in myeloperoxidase (MPO) infected with S. stercoralis had significantly decreased larval killing. It was concluded that there is redundancy in the primary immune response, with eosinophils killing the larvae through an MBP-dependent mechanism and neutrophils killing the worms through an MPO-dependent mechanism. Eosinophils are not required for the development or function of secondary immunity, but MPO from neutrophils is required for protective secondary immunity.
TL;DR: Investigation of the effect of PGE on human neutrophil reactive oxygen species (ROS) production in vitro and on LPS-induced lung inflammation in vivo in mice reveals that PGE inhibition of MPO activity by PGE could explain its anti-inflammatory action.
TL;DR: It is proposed that melatonin has a dual action as an effective anti-inflammatory and an antioxidant, and may be a hopeful therapeutic agent for UC.
Abstract: Increased free-radical production, decreased antioxidant capacity, and excessive inflammation are well-known features in the pathogenesis of inflammatory bowel disease. Melatonin is a powerful antioxidant and a scavenger of hydroxyl radicals. Melatonin has also been shown to have anti-inflammatory activities in tissues. Our study objective is to investigate the effects of melatonin on tissue inflammatory activities using an ulcerative colitis (UC) model induced by acetic acid (AA) in rats. Wistar rats (n = 32) were divided into four groups. AA-induced colitis was performed in two of the groups, while the other two groups were injected with saline intrarectally. One of the AA-induced colitis groups and one of the control groups were administered 100 mg/kg/day melatonin intraperitoneally, and the pair groups were given saline. After 4 days, colonic changes were evaluated biochemically by measuring proinflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6], myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) levels in tissue homogenates and by histopathological examination. AA caused colonic mucosal injury, whereas melatonin suppressed these changes in the AA-induced colitis group (P < 0.001). AA administration resulted in increased TNF-α, IL-1β, IL-6, MPO, and MDA levels, and decreased GSH and SOD levels, whereas melatonin administration reversed these effects (all P < 0.001). The present study proposes that melatonin has a dual action as an effective anti-inflammatory and an antioxidant, and may be a hopeful therapeutic agent for UC.
TL;DR: Plasma MPO concentrations provide independent prognostic value for the prediction of long-term incident MACEs in a stable, medically managed patient population with coronary artery disease.
Abstract: BACKGROUND: Myeloperoxidase (MPO) concentrations predict adverse clinical outcomes in the setting of acute coronary syndromes and heart failure, but the prognostic role of MPO in stable patients with known atherosclerotic burden is unclear.
METHODS: We examined plasma MPO concentrations and their relationship with prevalent significant coronary artery disease (defined as >50% stenosis in any coronary vessel) and incident major adverse cardiovascular events (MACEs), including death, myocardial infarction, and stroke, in a 3-year prospective follow-up study of 1895 patients undergoing elective coronary angiography.
RESULTS: The median plasma MPO concentration was 101 pmol/L (interquartile range 68–187 pmol/L). Patients with plasma MPO concentrations >322 pmol/L (14.6% of population) had increased risk of developing future MACEs [hazard ratio (HR) 1.78, 95% CI 1.33–2.37, P 322 pmol/L.
CONCLUSIONS: Plasma MPO concentrations provide independent prognostic value for the prediction of long-term incident MACEs in a stable, medically managed patient population with coronary artery disease. In individuals with increased hsCRP concentrations, we observed lower risk of incident MACEs when concomitant MPO concentrations were low vs when MPO concentrations were high.
TL;DR: The quantification of isoorientin in the extracts showed a correlation with their antioxidant activity, suggesting the potential of P. edulis rinds as functional food or as a possible source of natural flavonoids.
TL;DR: Positive correlation between thiobarbituric acid reactive species (TBARS) and markers of organ injury in lung and kidney was found and antioxidant effects seemed to depend not only on the diminution of oxidative damage but also on its anti-inflammatory activity.
TL;DR: The data indicate that anti-inflammatory and antioxidant effects, involve the inhibition of iNOS and TNF-alpha, among other properties, and these encourage clinical studies of these compounds for new therapeutic applications, especially those were inflammation plays a role.
Abstract: Aims and methods
Minocycline (Mino) and doxycycline (Dox) are second generation tetracyclines known to present several other effects, which are independent from their antimicrobial activities. We studied in a comparative way the anti-inflammatory effects of Mino and Dox, on acute models of peripheral inflammation in rodents (formalin test and peritonitis in mice, and carrageenan-induced paw oedema in rats). Immunohistochemical assays for TNF-alpha and iNOS in rat paws of carrageenan-induced oedema were also carried out as well as in vitro assays for myeloperoxidase (MPO) and lactate dehydrogenase (LDH). Furthermore, antioxidant activities were evaluated by the DPPH assay.
TL;DR: The brain’s production of cytokines and chemokines is an early event and it seemed to participate both in central nervous system (CNS) dysfunction and BBB permeability alterations, reinforcing the role of brain inflammatory response in the acute CNS dysfunction associated with sepsis.
Abstract: To evaluate the effects of sepsis on brain microvasculature leukocyte rolling and adherence, myeloperoxidase (MPO) activity, cytokine and chemokine concentrations, and behavioral screening 6, 12, and 24 h after sepsis induction. C57BL/6 mice or Wistar rats underwent cecal ligation and perforation (CLP) or sham operation. At 6, 12, and 24 h after sepsis induction, intravital microscopy was performed in the mice brain microvasculature to evaluate leukocyte rolling and adherence. Animals were killed and had the brain removed to determine MPO activity and the levels of cytokines and chemokines. A behavioral screening was also performed in a separate cohort of animals. Blood–brain barrier (BBB) permeability and cytokines and chemokines were determined in different brain regions in Wistar rats. There was a decrease in circulating leukocyte levels at 6, 12, and 24 h, an increase in rolling and adhesion of leukocytes in the brain microvasculature, followed by an increase in brain MPO activity. In addition, there was an increase in both brain cytokines and chemokines at different times. There was a decrease in the neuropsychiatric state muscle tone and strength only at 6 h, and a decrease in the autonomous function at 6 and 12 h. The pattern of brain cytokines and chemokines, and BBB permeability between the analyzed regions seemed to be similar with minor differences. During sepsis the brain’s production of cytokines and chemokines is an early event and it seemed to participate both in central nervous system (CNS) dysfunction and BBB permeability alterations, reinforcing the role of brain inflammatory response in the acute CNS dysfunction associated with sepsis.
TL;DR: EMPs contribute to lung injury through the initiation of a cytokine cascade that increases recruitment of neutrophils and subsequent release of MPO, suggesting that EMPs prime the lung for increased injury by other pathogens.
TL;DR: The findings of significantly elevated serum MMP-9, MPO, NE together with decreased TIMP-1 in smoker CP patients than non-smokers support that smoking together with periodontal destruction may expose/predispose to cardiovascular diseases.
Abstract: Oral Diseases (2010) 17, 68–76
Objectives: To investigate possible relationship between smoking and serum concentrations of matrix metalloproteinase-8,-9 (MMP-8, MMP-9), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), neutrophil elastase (NE), myeloperoxidase (MPO) in chronic periodontitis (CP) patients relative to periodontally healthy subjects.
Methods: Serum samples were obtained from 111 subjects before initiation of any periodontal intervention. Fifty-five CP patients (39 non-smokers, 16 smokers) and 56 periodontally healthy subjects (39 non-smokers, 17 smokers) were recruited. Serum concentrations of MMP-8 were determined by IFMA and MPO, MMP-9, TIMP-1, NE concentrations by ELISA. ANCOVA and Pearson correlation analysis was utilized for statistical analysis.
Results: Serum MPO, NE concentrations were higher in smoker CP than non-smoker CP patients (P = 0.002 and P 0.05). TIMP-1 concentration was higher in non-smoker CP than smoker CP group (P 0.05).
Conclusions: Our findings of significantly elevated serum MMP-9, MPO, NE together with decreased TIMP-1 in smoker CP patients than non-smokers support that smoking together with periodontal destruction may expose/predispose to cardiovascular diseases.
TL;DR: Findings show that (-)-α-bisabolol is able to decrease oxidative stress and inflammatory event associated with the lesions induced by ethanol, which is unrelated to the nitric oxide.
TL;DR: Increased expression of MPO in damaged rat and human liver is due to recruited elastase positive NGs, as demonstrated in normal rat liver and acutely injured human liver.
Abstract: Myeloperoxidase (MPO) is involved in acute and chronic inflammatory diseases. The source of MPO in acute liver diseases is still a matter of debate. Therefore, we analysed MPO-gene expression on sections from normal and acutely damaged [carbon tetrachloride-(CCl4) or whole liver γ-Irradiation] rat liver by immunohistochemistry, real time PCR and Western blot analysis of total RNA and protein. Also total RNA and protein from isolated Kupffer cells, hepatic stellate cells, Hepatocytes, endothelial cells and neutrophil granulocytes (NG) was analysed by real time PCR and Western blot, respectively. Sections of acutely injured human liver were prepared for MPO and CD68 immunofluorescence double staining. In normal rat liver MPO was detected immunohistochemically and by immunofluorescence double staining only in single NG. No MPO was detected in isolated parenchymal and non-parenchymal cell populations of the normal rat liver. In acutely damaged rat liver mRNA of MPO increased 2.8-fold at 24 h after administration of CCl4 and 3.3-fold at 3 h after γ-Irradiation and MPO was detected by immunofluorescence double staining only in elastase (NE) positive NGs but not in macrophages (ED1 or CD68 positive cells). Our results demonstrate that, increased expression of MPO in damaged rat and human liver is due to recruited elastase positive NGs.
TL;DR: The results suggest an important role of nitric oxide, via activation of iNOS, in the pathogenesis of intestinal mucositis, as indicated by the reduced villus and crypt damages, inflammatory alterations, cell death, MPO activity, and nitrotyrosine immunostaining due to MTX challenge.
Abstract: Background: Methotrexate treatment has been associated to intestinal epithelial damage. Studies have suggested an important role of nitric oxide in such injury. The aim of this study was to investigate the role of nitric oxide (NO), specifically iNOS on the pathogenesis of methotrexate (MTX)-induced intestinal mucositis. Methods: Intestinal mucositis was carried out by three subcutaneous MTX injections (2.5 mg/kg) in Wistar rats and in inducible nitric oxide synthase knock-out (iNOS -/- ) and wild-type (iNOS +/+ ) mice. Rats were treated intraperitoneally with the NOS inhibitors aminoguanidine (AG; 10 mg/Kg) or L-NAME (20 mg/Kg), one hour before MTX injection and daily until sacrifice, on the fifth day. The jejunum was harvested to investigate the expression of Ki67, iNOS and nitrotyrosine by immunohistochemistry and cell death by TUNEL. The neutrophil activity by myeloperoxidase (MPO) assay was performed in the three small intestine segments. Results: AG and L-NAME significantly reduced villus and crypt damages, inflammatory alterations, cell death, MPO activity, and nitrotyrosine immunostaining due to MTX challenge. The treatment with AG, but not L-NAME, prevented the inhibitory effect of MTX on cell proliferation. MTX induced increased expression of iNOS detected by immunohistochemistry. MTX did not cause significant inflammation in the iNOS -/- mice. Conclusion: These results suggest an important role of NO, via activation of iNOS, in the pathogenesis of intestinal mucositis.
TL;DR: In this article, the authors compared the natural healing process with biomembrane-based subcutaneous implant using biochemical and immunohistological assays, and found that natural latex biombrane (NLB) significantly induced the inflammatory phase of healing mediated by oxidative stress, which appeared to influence the subsequent phases such as angiogenesis and fibroplasia (independent of TGF-β1) without influencing collagenesis.
Abstract: The aim of the present study was to compare healing obtained with biomembranes with the natural healing process (sham) using biochemical and immunohistological assays. C57BL/6 mice were divided into 4 groups of 15 mice each and received different subcutaneous implants: natural latex biomembrane (NLB), denatured latex (DL), expanded polytetrafluorethylene (ePTFE), or sham. On the 2nd, 7th, and 14th days post-treatment, 5 mice per group were sacrificed and biopsied for the following measurements: oxidative stress based on malondialdehyde (MDA), myeloperoxidase (MPO) and hydrogen peroxide by the method of ferrous oxidation-xylenol orange (FOX), as well as glutathione and total proteins; histological evaluation to enumerate inflammatory cells, fibroblasts, blood vessels, and collagen, and immunohistochemical staining for inducible nitric oxide synthase, interleukin-1β, vascular endothelial growth factor (VEGF), and transforming growth factor-β1 (TGF-β1). On day 2 post-treatment, NLB stimulated a dense inflammatory infiltrate mainly consisting of polymorphonuclear cells, as indicated by increased MPO (P < 0.05), but oxidative stress due to MDA was not observed until the 7th day (P < 0.05). The number of blood vessels was greater in NLB (P < 0.05) and DL (P < 0.05) mice compared to sham animals on day 14. NLB induced fibroplasia by day 14 (P < 0.05) with low expression of TGF-β1 and collagenesis. Thus, NLB significantly induced the inflammatory phase of healing mediated by oxidative stress, which appeared to influence the subsequent phases such as angiogenesis (with low expression of VEGF) and fibroplasia (independent of TGF-β1) without influencing collagenesis.