scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Phosphatidylserine-containing liposomes suppress inflammatory bone loss by ameliorating the cytokine imbalance provoked by infiltrated macrophages.

01 Jun 2011-Laboratory Investigation (Nature Publishing Group)-Vol. 91, Iss: 6, pp 921-931
TL;DR: PSL-induced different influence on the activities of p38 MAPK and ERK is a likely underlying mechanism for phenotypic change of infiltrated macrophages after the phagocytosis of PSLs, resulting in the inhibition of inflammatory bone loss.
About: This article is published in Laboratory Investigation.The article was published on 2011-06-01 and is currently open access. It has received 52 citations till now. The article focuses on the topics: Interleukin 10 & Phagocytosis.
Citations
More filters
Journal ArticleDOI
TL;DR: The restorative macrophage phenotype was recapitulated in vitro by the phagocytosis of cellular debris with associated activation of the ERK signaling cascade, offering a therapeutic strategy to this orphan pathological process.
Abstract: Although macrophages are widely recognized to have a profibrotic role in inflammation, we have used a highly tractable CCl4-induced model of reversible hepatic fibrosis to identify and characterize the macrophage phenotype responsible for tissue remodeling: the hitherto elusive restorative macrophage. This CD11Bhi F4/80int Ly-6Clo macrophage subset was most abundant in livers during maximal fibrosis resolution and represented the principle matrix metalloproteinase (MMP) -expressing subset. Depletion of this population in CD11B promoter–diphtheria toxin receptor (CD11B-DTR) transgenic mice caused a failure of scar remodeling. Adoptive transfer and in situ labeling experiments showed that these restorative macrophages derive from recruited Ly-6Chi monocytes, a common origin with profibrotic Ly-6Chi macrophages, indicative of a phenotypic switch in vivo conferring proresolution properties. Microarray profiling of the Ly-6Clo subset, compared with Ly-6Chi macrophages, showed a phenotype outside the M1/M2 classification, with increased expression of MMPs, growth factors, and phagocytosis-related genes, including Mmp9, Mmp12, insulin-like growth factor 1 (Igf1), and Glycoprotein (transmembrane) nmb (Gpnmb). Confocal microscopy confirmed the postphagocytic nature of restorative macrophages. Furthermore, the restorative macrophage phenotype was recapitulated in vitro by the phagocytosis of cellular debris with associated activation of the ERK signaling cascade. Critically, induced phagocytic behavior in vivo, through administration of liposomes, increased restorative macrophage number and accelerated fibrosis resolution, offering a therapeutic strategy to this orphan pathological process.

744 citations


Cites background from "Phosphatidylserine-containing lipos..."

  • ...Furthermore, recent studies have shown that liposome administration can alter macrophage phenotype in vivo in part by induction of ERK signaling after ingestion (53, 54)....

    [...]

Journal ArticleDOI
TL;DR: This review summarizes new data on inflammatory bone loss obtained in 2011 and describes the molecular pathways by which receptor activator of nuclear factor-κB ligand and RANKL induce osteoclast differentiation.
Abstract: Chronic inflammation including autoimmune disease is an important risk factor for the development of osteoporosis. Receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) play a central role in osteoclast differentiation and function, and the molecular pathways by which M-CSF and RANKL induce osteoclast differentiation have been analyzed in detail. Proinflammatory cytokines directly or indirectly regulate osteoclastogenesis and bone resorption providing a link between inflammation and osteoporosis. Tumor necrosis factor-α, interleukin (IL)-1, IL-6, and IL-17 are the most important proinflammatory cytokines triggering inflammatory bone loss. Inhibition of these cytokines has provided potent therapeutic effects in the treatment of diseases such as rheumatoid arthritis. Further investigation is needed to understand the pathophysiology and to develop new strategies to treat inflammatory bone loss. This review summarizes new data on inflammatory bone loss obtained in 2011.

152 citations


Cites background from "Phosphatidylserine-containing lipos..."

  • ...[77] suggests that this effect is due to increased IL-10 production by macrophages....

    [...]

Journal ArticleDOI
13 Feb 2014-Viruses
TL;DR: The induction of a uniquely polarized macrophage subset from infected monocytes is described, which is argued to be the ideal cellular environment for the initiation of viral gene expression and replication and, ultimately, viral spread and persistence within the infected host.
Abstract: The wide range of disease pathologies seen in multiple organ sites associated with human cytomegalovirus (HCMV) infection results from the systemic hematogenous dissemination of the virus, which is mediated predominately by infected monocytes. In addition to their role in viral spread, infected monocytes are also known to play a key role in viral latency and life-long persistence. However, in order to utilize infected monocytes for viral spread and persistence, HCMV must overcome a number of monocyte biological hurdles, including their naturally short lifespan and their inability to support viral gene expression and replication. Our laboratory has shown that HCMV is able to manipulate the biology of infected monocytes in order to overcome these biological hurdles by inducing the survival and differentiation of infected monocytes into long-lived macrophages capable of supporting viral gene expression and replication. In this current review, we describe the unique aspects of how HCMV promotes monocyte survival and differentiation by inducing a “finely-tuned” macrophage cell type following infection. Specifically, we describe the induction of a uniquely polarized macrophage subset from infected monocytes, which we argue is the ideal cellular environment for the initiation of viral gene expression and replication and, ultimately, viral spread and persistence within the infected host.

70 citations

Journal ArticleDOI
TL;DR: The data show that myelin modulates the phenotype of macrophages by PPAR activation, which may subsequently dampen MS lesion progression and the immunoregulatory impact of naturally-occurring myelin lipids may hold promise for future MS therapeutics.
Abstract: Foamy macrophages, containing myelin degradation products, are abundantly found in active multiple sclerosis (MS) lesions. Recent studies have described an altered phenotype of macrophages after myelin internalization. However, mechanisms by which myelin affects the phenotype of macrophages and how this phenotype influences lesion progression remain unclear. We demonstrate that myelin as well as phosphatidylserine (PS), a phospholipid found in myelin, reduce nitric oxide production by macrophages through activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ). Furthermore, uptake of PS by macrophages, after intravenous injection of PS-containing liposomes (PSLs), suppresses the production of inflammatory mediators and ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The protective effect of PSLs in EAE animals is associated with a reduced immune cell infiltration into the central nervous system and decreased splenic cognate antigen specific proliferation. Interestingly, PPARβ/δ is activated in foamy macrophages in active MS lesions, indicating that myelin also activates PPARβ/δ in macrophages in the human brain. Our data show that myelin modulates the phenotype of macrophages by PPAR activation, which may subsequently dampen MS lesion progression. Moreover, our results suggest that myelin-derived PS mediates PPARβ/δ activation in macrophages after myelin uptake. The immunoregulatory impact of naturally-occurring myelin lipids may hold promise for future MS therapeutics.

64 citations


Cites background from "Phosphatidylserine-containing lipos..."

  • ...In vivo, PSLs have been described to promote the resolution of inflammation by modulating macrophage function in a model for inflammatory bone loss and myocardial infarction [31,33]....

    [...]

  • ...In vitro, clearance of apoptotic cells and PSLs skews macrophages towards a tolerogenic phenotype [21,23,29-35]....

    [...]

Journal ArticleDOI
TL;DR: The findings suggest that the PSL-IL10 has macrophage targeting ability and enhanced anti- inflammatory effect due to the synergistic anti-inflammatory effects of IL-10 and PSL, and can be used as amacrophage-targeted therapeutic material for inflammation-related diseases, including obesity.

55 citations

References
More filters
Journal ArticleDOI
TL;DR: The up-regulation of terminal PGESs that are preferentially coupled with COX-1, especially mPGES-2, plays the pivotal role in PS liposome-induced PGE2 production by microglia, and other PS-recognizing receptors could also promote PGE 2 production by transducing intracellular signals including p44/p42 ERK after PSliposomes treatment.

49 citations


"Phosphatidylserine-containing lipos..." refers methods in this paper

  • ...The PSL-treated or untreated macrophage extracts were prepared with cell lysis buffer as described previously.(13) A...

    [...]

  • ...PSLs and PCLs were prepared as described previously.(13) In some experiments,...

    [...]

Journal ArticleDOI
TL;DR: There are critical cytokine interactions linking hIFN-γ+ Th1 cells to RANKL-RANK/OPG signaling for periodontal osteoclastogenesis in vivo.
Abstract: To study anti-inflammatory cytokine effects on RANKL+-T-cell-mediated osteoclastogenesis in vivo, we injected human interleukin-10 (hIL-10) into pathogen-infected HuPBL-NOD/SCID mice. The results show significantly decreased RANKL+ Th1-associated alveolar bone loss and coexpression of human gamma interferon (hIFN-γ) and human macrophage colony-stimulating factor, but not hIL-4, in RANKL+ Th cells compatible with those from successfully treated aggressive periodontitis subjects. Thus, there are critical cytokine interactions linking hIFN-γ+ Th1 cells to RANKL-RANK/OPG signaling for periodontal osteoclastogenesis in vivo.

49 citations


"Phosphatidylserine-containing lipos..." refers background in this paper

  • ...Among anti-inflammatory mediators, including TGF-b1 and PGE2, IL-10 is known as the strongest feedback mediator of inflammatory bone loss.(23,24)...

    [...]

Journal ArticleDOI
TL;DR: IL-17 is highly produced by αβT cells in the early phase of EAM hearts and IL-17 inhibition might be a possible mechanism of the amelioration of E AM by IL-10-Ig treatment, suggesting that IL- 17 produced by Th17 plays an important role in the pathogenesis of rat EAM.
Abstract: Background T-helper (Th)1/Th2 cytokine balance plays an important role in the pathogenesis of myocarditis. Recently, some studies indicate that interleukin (IL)-17, known as a T cell (Th17)-derived proinflammatory cytokine, is the major mediator of tissue inflammation in inflammatory and autoimmune diseases. Experimental autoimmune myocarditis (EAM) is a T cell-mediated autoimmune disease; however, the pathogenic role of IL-17 in the development of rat EAM remains largely unknown. Methods and Results In the present study, alterations of IL-17-related protein expressions were investigated and then the effect of hydrodynamic-based delivery of plasmid DNA encoding the IL-10-Ig gene on rat EAM and the effect of IL-10-Ig on IL-17 was evaluated. The results showed that IL-17 was expressed more highly than IFN-γ expressed by Th1 cells in αβT cells and the peaks of IL-17 related protein expression in the heart were the early phase of EAM. Moreover, we observed that IL-10-Ig gene therapy was effective in controlling EAM and that IL-10-Ig significantly suppressed the expression of IL-17 as well as other proinflammatory cytokines, IL-1β and TNF-α, in IL-1-stimulated splenocytes cultured from EAM rats. Conclusions IL-17 is highly produced by αβT cells in the early phase of EAM hearts and IL-17 inhibition might be a possible mechanism of the amelioration of EAM by IL-10-Ig treatment. These data suggest that IL-17 produced by Th17 plays an important role in the pathogenesis of rat EAM. (Circ J 2008; 72: 813 - 819)

47 citations

Journal ArticleDOI
TL;DR: TGF-beta is the factor produced by PS-liposomes that suppresses production of NO, and the ERK signaling pathway is intimately involved in TGF- beta production by macrophages following treatment with PS- Liposomes.

43 citations

Journal ArticleDOI
TL;DR: Apoptotic thymocytes inactivate the aminophospholipid translocase and activate the scramblase, which randomizes phospholipids across the membrane and brings PS to the cell surface, which is as necessary for apoptotic cell engulfment as is recognition of PS on the target cell surface.
Abstract: Apoptotic thymocytes inactivate the aminophospholipid translocase, which transports phosphatidylserine (PS) to the inner leaflet of the plasma membrane, and activate the scramblase, which randomizes phospholipids across the membrane and brings PS to the cell surface. Although different macrophages use at least two different systems to recognize and engulf apoptotic thymocytes, both systems recognize PS on the apoptotic target. Thymocytes treated with Ca2+ and ionophore to inactivate the translocase and activate the scramblase immediately expose PS on their surface and are immediately recognized and phagocytosed. These targets, on which PS has been artificially exposed, are recognized by the PS exposed on their surface. However, they apparently also engage the vitronectic receptor, a lectin-like receptor and CD14. All of these receptors are implicated in the phagocytosis of apoptotic thymocytes, suggesting that loss of asymmetry and/or exposure of PS is sufficient to generate the ligands recognized by those receptors. The role of PS is not confined to the target cell surface, however. PS is constitutively exposed on the surface of macrophages and is as necessary for apoptotic cell engulfment as is recognition of PS on the target cell surface.

42 citations