scholarly journals Neutrophil-derived leukotriene B4 is required for inflammatory arthritis

2006 ◽  
Vol 203 (4) ◽  
pp. 837-842 ◽  
Author(s):  
Mei Chen ◽  
Bing K. Lam ◽  
Yoshihide Kanaoka ◽  
Peter A. Nigrovic ◽  
Laurent P. Audoly ◽  
...  
Keyword(s):  
Inflammatory Arthritis ◽  
Leukotriene B4 ◽  
Transfer Model ◽  
Effector Functions ◽  
Serum Transfer ◽  
Cellular Source ◽  
Disease Induction ◽  
Deficient Mice ◽  
Arthritis Susceptibility ◽  
Serum Transfer Model

Neutrophils serve as a vanguard of the acute innate immune response to invading pathogens. Neutrophils are also abundant at sites of autoimmune inflammation, such as the rheumatoid joint, although their pathophysiologic role is incompletely defined and relevant effector functions remain obscure. Using genetic and pharmacologic approaches in the K/BxN serum transfer model of arthritis, we find that autoantibody-driven erosive synovitis is critically reliant on the generation of leukotrienes, and more specifically on leukotriene B4 (LTB4), for disease induction as well as perpetuation. Pursuing the cellular source for this mediator, we find via reconstitution experiments that mast cells are a dispensable source of leukotrienes, whereas arthritis susceptibility can be restored to leukotriene-deficient mice by intravenous administration of wild-type neutrophils. These experiments demonstrate a nonredundant role for LTB4 in inflammatory arthritis and define a neutrophil mediator involved in orchestrating the synovial eruption.

scholarly journals TRANCE/RANKL Knockout Mice Are Protected from Bone Erosion in a Serum Transfer Model of Arthritis

2001 ◽  
Vol 159 (5) ◽  
pp. 1689-1699 ◽  
Author(s):  
Allison R. Pettit ◽  
Hong Ji ◽  
Dietrich von Stechow ◽  
Ralph Müller ◽  
Steven R. Goldring ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Bone Erosion ◽  
Transfer Model ◽  
Serum Transfer ◽  
Serum Transfer Model

scholarly journals Low-Dose Radiotherapy Leads to a Systemic Anti-Inflammatory Shift in the Pre-Clinical K/BxN Serum Transfer Model and Reduces Osteoarthritic Pain in Patients

2022 ◽  
Vol 12 ◽  
Author(s):  
Thomas Weissmann ◽  
Michael Rückert ◽  
Jian-Guo Zhou ◽  
Michaela Seeling ◽  
Sebastian Lettmaier ◽  
...  
Keyword(s):  
Mouse Model ◽  
Molecular Mechanisms ◽  
Low Dose ◽  
Transfer Model ◽  
Clinical Approach ◽  
Analgesic Effects ◽  
Low Dose Radiotherapy ◽  
Serum Transfer ◽  
Highly Effective ◽  
Serum Transfer Model

Osteoarthritis (OA) is the leading degenerative joint disease in the western world and leads, if left untreated, to a progressive deterioration of joint functionality, ultimately reducing quality of life. Recent data has shown, that especially OA of the ankle and foot are among the most frequently affected regions. Current research in OA points towards a complex involvement of various cell and tissue types, often accompanied by inflammation. Low-dose radiotherapy (LDRT) is widely used for the treatment of degenerative and inflammatory diseases. While the reported analgesic effects are well known, the underlying molecular mechanisms are only poorly understood. We therefore correlated a clinical approach, looking at pain reduction in 196 patients treated with LDRT with a pre-clinical approach, utilizing the K/BxN serum transfer mouse model using flow cytometry and multiplex ELISA for analysis. While an improvement of symptoms in the majority of patients was found, patients suffering from symptoms within the tarsi transversa show a significantly lower level of improvement. Further, a significant impact of therapy success was detected depending on whether only one or both feet were affected. Further, patients of younger age showed a significantly better outcome than older ones while needing fewer treatment series. When looking on a cellular level within the mouse model, a systemic alteration of immune cells namely a shift from CD8+ to CD4+ T cells and reduced numbers of DCs was observed. A general reduction of inflammatory cytokines was detected, with significant alterations in IL-4 and IL-17 levels, all of which could potentially be responsible for the highly effective clinical improvement in patients. Taken together our data indicate that LDRT can be regarded as a highly effective treatment option for patients suffering from OA of the foot and ankle, in terms of analgesic effects, especially in younger patients. Furthermore, the observed effects are mediated by an interplay of cellular and soluble immune factors, as observed in the K/BxN serum transfer model. With this interdisciplinary approach we aim to encourage the usage of LDRT as an additive treatment strategy not only as a last resort, but also earlier in the course of disease.

Gene targeting of properdin ameliorates disease development in the K/BxN mouse serum transfer model of arthritis

2008 ◽  
Vol 45 (16) ◽  
pp. 4112
Author(s):  
Yuko Kimura ◽  
Lin Zhou ◽  
David Kim ◽  
Takashi Miwa ◽  
Wen-Chao Song
Keyword(s):  
Gene Targeting ◽  
Mouse Serum ◽  
Transfer Model ◽  
Disease Development ◽  
Serum Transfer ◽  
Serum Transfer Model

scholarly journals 5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via a BLTR1 signaling axis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jong Min Choi ◽  
Seung Eun Baek ◽  
Ji On Kim ◽  
Eun Yeong Jeon ◽  
Eun Jeong Jang ◽  
...  
Keyword(s):  
Tissue Injury ◽  
Vascular Inflammation ◽  
High Mobility ◽  
Leukotriene B4 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Signaling Axis ◽  
Cellular Source ◽  
Leukotriene Receptor ◽  
In Cells

AbstractMonocyte chemoattractant protein-1 (MCP-1) plays an important role in initiating vascular inflammation; however, its cellular source in the injured vasculatures is unclear. Given the importance of high mobility group box 1 (HMGB1) in tissue injury, we investigated the role of vascular smooth muscle cells (VSMCs) in MCP-1 production in response to HMGB1. In primary cultured rat aortic VSMCs stimulated with HMGB1, the expression of MCP-1 and 5-lipoxygenase (LO) was increased. The increased MCP-1 expression in HMGB1 (30 ng/ml)-stimulated cells was significantly attenuated in 5-LO-deficient cells as well as in cells treated with zileuton, a 5-LO inhibitor. Likewise, MCP-1 expression and production were also increased in cells stimulated with exogenous leukotriene B4 (LTB4), but not exogenous LTC4. LTB4-induced MCP-1 expression was attenuated in cells treated with U75302, a LTB4 receptor 1 (BLTR1) inhibitor as well as in BLTR1-deficient cells, but not in 5-LO-deficient cells. Moreover, HMGB1-induced MCP-1 expression was attenuated in BLTR1-deficient cells or by treatment with a BLTR1 inhibitor, but not other leukotriene receptor inhibitors. In contrast to MCP-1 expression in response to LTB4, the increased MCP-1 production in HMGB1-stimulated VSMC was markedly attenuated in 5-LO-deficient cells, indicating a pivotal role of LTB4-BLTR1 signaling in MCP-1 expression in VSMCs. Taken together, 5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via BLTR1 signaling, suggesting the LTB4-BLTR1 signaling axis as a potential therapeutic target for vascular inflammation in the injured vasculatures.

scholarly journals Tissue-specific expression of B7x protects from CD4 T cell–mediated autoimmunity

2011 ◽  
Vol 208 (8) ◽  
pp. 1683-1694 ◽  
Author(s):  
Joyce Wei ◽  
P’ng Loke ◽  
Xingxing Zang ◽  
James P. Allison
Keyword(s):  
T Cells ◽  
Pancreatic Islets ◽  
Peripheral Tolerance ◽  
Wild Type ◽  
Autoimmune Encephalomyelitis ◽  
Specific Expression ◽  
Tissue Specific ◽  
Disease Induction ◽  
Deficient Mice ◽  
Experimental Autoimmune

B7x, an inhibitory member of the B7/CD28 superfamily, is highly expressed in a broad range of nonhematopoietic organs, suggesting a role in maintaining peripheral tolerance. As endogenous B7x protein is expressed in pancreatic islets, we investigated whether the molecule inhibits diabetogenic responses. Transfer of disease-inducing BDC2.5 T cells into B7x-deficient mice resulted in a more aggressive form of diabetes than in wild-type animals. This exacerbation of disease correlated with higher frequencies of islet-infiltrating Th1 and Th17 cells. Conversely, local B7x overexpression inhibited the development of autoimmunity, as crossing diabetes-susceptible BDC2.5/B6g7 mice to animals overexpressing B7x in pancreatic islets abrogated disease induction. This protection was caused by the inhibition of IFN-γ production by CD4 T cells and not to a skewing or expansion of Th2 or regulatory T cells. The suppressive function of B7x was also supported by observations from another autoimmune model, experimental autoimmune encephalomyelitis, in which B7x-deficient mice developed exacerbated disease in comparison with wild-type animals. Analysis of central nervous system–infiltrating immune cells revealed that the loss of endogenous B7x resulted in expanded Th1 and Th17 responses. Data from these two autoimmune models provide evidence that B7x expression in the periphery acts as an immune checkpoint to prevent tissue-specific autoimmunity.

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