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- W4313385094 abstract "Abstract Mycoplasma arthritidis mitogen (MAM), a potent superantigen (SAg) secreted by M. arthritidis, is known to contribute to arthritis in mouse models of human rheumatoid arthritis (RA). Type I interferons (IFNs) are known to play an important role in RA. IFN gene transcription is activated by IFN-regulatory factors (IRFs) in response to innate immune recognition. We previously demonstrated that mouse strains with differing expression of the innate immune receptor TLR4 or/and TLR2 differ in their response to MAM. In this study, we investigated if MAM, or MAM with an autoantigen collagen II, can stimulate synovial fibroblasts (SF) to mount inflammatory responses in a mouse arthritis model. We found that in vitro stimulation of naïve SF with MAM in an arthritis susceptible mouse strain greatly increased level of IRF7 and IFNα. HMGB1, a heat-shock stress protein was also detected to produce in the cell culture of MAM-stimulated SF. In vivo studies showed mice injected with CII and MAM developed severe arthritis and exhibited a high HMGB1 level. An increased HMGB1 level was linked to the upregulation of the intracellular IRF7 and IFNα, and IRF7 was effectively inhibited by an anti-HMGB1 treatment, suggesting HMGB1 dependence. This led to the reduction of inflammatory mediators IL-6 and MMPs in inflamed joints of arthritis mice. Thus, our results suggest that MAM is capable of selecting the SF for local joint inflammation by promoting HMGB1 and IRF7 following interaction with TLR4. Our findings clearly demonstrates microbial agents, such as MAM SAg, can modify host tissue components, such as CII and stimulate synoviocytes, thus promoting local joint inflammation in autoimmune arthritis." @default.
- W4313385094 created "2023-01-06" @default.
- W4313385094 creator A5001928069 @default.
- W4313385094 creator A5018287585 @default.
- W4313385094 date "2017-05-01" @default.
- W4313385094 modified "2023-09-27" @default.
- W4313385094 title "Engagement of TLR4 with MAM superantigen promotes HMGB1-mediated induction of IRF7 and IFNα in synoviocytes of a mouse model of human RA" @default.
- W4313385094 doi "https://doi.org/10.4049/jimmunol.198.supp.55.11" @default.
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