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Induction of arthri...
Induction of arthritis by high mobility group box-1 protein is independent of tumour necrosis factor signalling.
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- Pullerits, Rille, 1969 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Jonsson, Ing-Marie, 1949 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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Kollias, George (författare)
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- Tarkowski, Andrej, 1951 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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(creator_code:org_t)
- Springer Science and Business Media LLC, 2008
- 2008
- Engelska.
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Ingår i: Arthritis research & therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 10:3
- Relaterad länk:
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https://arthritis-re...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- ABSTRACT: INTRODUCTION: TNFalpha and HMGB1 are two potent pro-inflammatory cytokines implicated as important mediators of arthritis. Increased levels of these cytokines are found in the joints of RA patients and they trigger arthritis when applied into the joints of naive mice. HMGB1 is actively released from immune cells in response to TNFalpha and once released, it induces in turn production of several pro-inflammatory cytokines including IL-6 and TNFalpha by macrophages. However, it is unknown whether HMGB1-induced arthritis is mediated via TNFalpha pathway. The purpose of this study was to investigate whether the arthritis-inducing effect of HMGB1 is dependent on TNFalpha expression in vivo and to assess whether TNFalpha deficiency affects a pro-inflammatory cytokine response to HMGB1 in vitro. METHODS: TNFalpha knockout (KO) mice and backcrossed control animals on C57Bl6 background were injected intra-articularly (i.a.) with 5 micrograms of HMGB1. Joints were dissected three days after i.a. injection and evaluated histologically by scoring the frequency and severity of arthritis. For in vitro studies, mouse spleen cultures from TNFalpha KO and control mice were incubated with different doses of HMGB1and cell culture supernatants were collected at different time points for analysis of IL-6. RESULTS: I.a. injection of HMGB1 into healthy mouse joints resulted in overall frequency of 32-39 % arthritic animals. No significant differences were found with respect to severity and incidence of synovitis between mice deficient for TNFalpha (7 out of 18 mice with arthritis) in comparison with control TNFalpha+/+ animals (6 out of 19). No significant differences were detected between spleen cells from TNFalpha+/+ versus TNFalpha-/- mice regarding IL-6 production upon stimulation with highly purified HMGB1 following 24 and 48 hours. However, upon stimulation with suboptimal dose of recombinant HMGB1, the splenocytes from TNFalpha+/+ animals released significantly more IL-6 than cells from the knockout mice (602 +/- 112 and 304 +/- 50 pg/ml, respectively, p< 0.05). CONCLUSIONS: Our data show that HMGB1 triggered joint inflammation is not mediated via TNF pathway. Combined with our previous study, we suggest that HMBG1-triggered arthritis is likely to be mediated through IL-1 activation.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- HMGB1
- TNFalpha
- arthritis
- cytokines
- knockout mice
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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