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Littermate Mice (littermate + mouse)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

MAPK3 deficiency drives autoimmunity via DC arming

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2010
Ivo Bendix
Abstract DC are professional APC that instruct T cells during the inflammatory course of EAE. We have previously shown that MAPK3 (Erk1) is important for the induction of T-cell anergy. Our goal was to determine the influence of MAPK3 on the capacity of DC to arm T-cell responses in autoimmunity. We report that DC from Mapk3,/, mice have a significantly higher membrane expression of CD86 and MHC-II and , when loaded with the myelin oligodendrocyte glycoprotein , show a superior capacity to prime naïve T cells towards an inflammatory phenotype than Mapk3+/+ DC. Nonetheless and as previously described, Mapk3,/, mice were only slightly but not significantly more susceptible to myelin oligodendrocyte glycoprotein-induced EAE than WT littermate mice. However, Mapk3+/+ mice engrafted with Mapk3,/, BM (KO,WT) developed a severe form of EAE, in direct contrast to WT,KO mice, which were even less sick than control WT,WT mice. An infiltration of DC and accumulation of Th17 cells was also observed in the CNS of KO,WT mice. Therefore, triggering of MAPK3 in the periphery might be a therapeutic option for the treatment of neuroinflammation since absence of this kinase in the immune system leads to severe EAE. [source]

Transthyretin enhances nerve regeneration

JOURNAL OF NEUROCHEMISTRY, Issue 2 2007
Carolina E. Fleming
Abstract Mutations in transthyretin (TTR) are associated with familial amyloid polyneuropathy, a neurodegenerative disorder characterized by TTR deposition in the PNS. The aim of this study was to unravel whether TTR has a role in nerve physiology that could account for its preferential accumulation in the PNS, when mutated. The sensorimotor performance of wild-type and TTR knockout (KO) littermate mice was compared and showed impairment in mice lacking TTR. Given the possibility that, upon regeneration, the consequences arising from TTR absence might be exacerbated, nerve crush was performed in both strains. TTR KO mice presented delayed functional recovery resulting from decreased number of myelinated and unmyelinated fibers. Moreover, in transgenic mice in a TTR KO background, expressing human TTR in neurons, this phenotype was rescued, reinforcing that TTR enhances nerve regeneration. In vitro assays showed that neurite outgrowth and extension were decreased in the absence of TTR, probably underlying the decreased number of regenerating axons in TTR KO mice. Our findings demonstrate that TTR participates in nerve physiology and that it enhances nerve regeneration. Moreover, the assignment of a TTR function in nerve biology and repair, may explain its preferential deposition, when mutated, in the PNS of familial amyloid polyneuropathy patients. [source]

Endogenous estrogen regulation of inflammatory arthritis and cytokine expression in male mice, predominantly via estrogen receptor ,

ARTHRITIS & RHEUMATISM, Issue 4 2010
Y. H. Yang
Objective A number of experimental observations have associated elevated estrogen levels with amelioration of inflammation. The involvement of estrogen and estrogen receptor (ER) isotypes in the regulation of inflammation in males is not well understood. In this study, we used specific ER, and ER, agonists in male mice deficient in estrogen because of a deletion of aromatase (aromatase-knockout [ArKO] mice) to investigate ER isotype utilization in estrogen regulation of inflammation. Methods Lipopolysaccharide (LPS)-induced cytokine expression and antigen-induced arthritis (AIA) were investigated in male ArKO and WT littermate mice, as well as in response to selective agonists of ER, (16,-LE2) and ER, (8,-VE2). The therapeutic effect of selective ER agonists was also examined in mice with collagen-induced arthritis (CIA). Results Estrogen deficiency in ArKO mice was associated with significant increases in LPS-induced serum interleukin-6 (IL-6), tumor necrosis factor, monocyte chemotactic protein 1, and interferon-, levels, which were significantly abrogated by administration of 16,-LE2, but not 8,-VE2. In contrast, both 16,-LE2 and 8,-VE2 significantly increased LPS-induced IL-10 levels. Estrogen deficiency was also associated with significant exacerbation of AIA and antigen-specific T cell proliferation, which was reversed by administration of either 16,-LE2 or 8,-VE2. ArKO mice showed increased antigen-specific T cell proliferation in response to immunization with type II collagen (CII). Administration of 16,-LE2, but not 8,-VE2, significantly reduced the severity of CIA, which was associated with inhibition of anti-CII,specific IgG. Conclusion These data indicate that endogenous estrogen plays an essential inhibitory role in inflammation in male mice and that ER, is the dominant receptor that mediates these effects. [source]

Adenosine A2A receptors in diffuse dermal fibrosis: Pathogenic role in human dermal fibroblasts and in a murine model of scleroderma

ARTHRITIS & RHEUMATISM, Issue 8 2006
E. S. L. Chan
Objective Adenosine regulates inflammation and tissue repair, and adenosine A2A receptors promote wound healing by stimulating collagen matrix production. We therefore examined whether adenosine A2A receptors contribute to the pathogenesis of dermal fibrosis. Methods Collagen production by primary human dermal fibroblasts was analyzed by real-time polymerase chain reaction, 14C-proline incorporation, and Sircol assay. Intracellular signaling for dermal collagen production was investigated using inhibitors of MEK-1 and by demonstration of ERK phosphorylation. In vivo effects were studied in a bleomycin-induced dermal fibrosis model using adenosine A2A receptor,deficient wild-type littermate mice, C57BL/6 mice, and mice treated with adenosine A2A receptor antagonist. Morphometric features and levels of hydroxyproline were determined as measures of dermal fibrosis. Results Adenosine A2A receptor occupancy promoted collagen production by primary human dermal fibroblasts, which was blocked by adenosine A2A, but not A1 or A2B, receptor antagonism. Adenosine A2A receptor ligation stimulated ERK phosphorylation, and A2A receptor,mediated collagen production by dermal fibroblasts was blocked by MEK-1 inhibitors. Adenosine A2A receptor,deficient and A2A receptor antagonist,treated mice were protected from developing bleomycin-induced dermal fibrosis. Conclusion These results demonstrate that adenosine A2A receptors play an active role in the pathogenesis of dermal fibrosis and suggest a novel therapeutic target in the treatment and prevention of dermal fibrosis in diseases such as scleroderma. [source]