PReS-FINAL-2085: The p38-mediated rapid downregulation of cell surface gp130 expression impairs IL-6 signaling in the synovial fluid of juvenile idiopathic arthritis patients
نویسندگان
چکیده
Results The level of cell surface gp130 expression on SF monocytes was reduced compared to peripheral blood (PB) monocytes from patients with JIA. This reduction could be reproduced by stimulating PB monocytes from healthy donors with SF and was dependent on p38 MAPK. The induction of p38 by IL-1b in PB monocytes interfered with IL-6 signaling due to the reduced cell surface expression of gp130. Conclusion The results suggest that p38-mediated pro-inflammatory stimuli induce the downregulation of gp130 on monocytes and thus restrict gp130-mediated signal transduction. This regulatory mechanism could be relevant in the inflamed joints of patients with JIA.
منابع مشابه
PReS-FINAL-2020: Cell type specific transcriptome analysis in patients with enthesitis related arthritis category of juvenile idiopathic arthritis (JIA-ERA)
Introduction Enthesitis Related Arthritis Category of Juvenile Idiopathic Arthritis (JIA-ERA) is the most common category of JIA seen in Asian Indians. Transcriptome analysis is a useful tool to analyse pathways involved in disease pathogenesis. Peripheral blood mononuclear cells (PBMC) and SFMC analysis showed involvement of innate immune cells in JIA-ERA. However PBMC/SFMC have variable numbe...
متن کاملPReS-FINAL-1003: Intrinsic cd4 and cd8 effector t cell resistance to suppression in the synovial fluid of juvenile idiopathic arthritis patients
Introduction Autoimmune diseases are characterized by an imbalance between regulatory T cells (Treg) and effector T cells (Teff) both in terms of number and function. Our group previously showed that Teff from the site of inflammation (i.e. synovial fluid, SF) of patients affected by Juvenile Idiopathic Arthritis (JIA) are resistant to autologous Treg-mediated suppression irrespective of the so...
متن کاملPReS-FINAL-1001: Lymphocytes from the inflamed joint of juvenile idiopathic arthritis patients express reduced levels of cd73 and have a functional defect in adenosine production
Introduction The nucleotidases CD39 and CD73 are responsible for the catabolism of pro-inflammatory ATP to AMP, and the consequent dephosphorylation of this nucleotide to regulatory adenosine. CD39 protein has previously been observed to be elevated (1) on JIA (Juvenile Idiopathic Arthritis) SFMC (synovial fluid mononuclear cells) with a correspondent increase in ATPase activity, while CD73 has...
متن کاملNerve growth factor downregulates inflammatory response in human monocytes through TrkA.
Nerve growth factor (NGF) levels are highly increased in inflamed tissues, but their role is unclear. We show that NGF is part of a regulatory loop in monocytes: inflammatory stimuli, while activating a proinflammatory response through TLRs, upregulate the expression of the NGF receptor TrkA. In turn, NGF, by binding to TrkA, interferes with TLR responses. In TLR-activated monocytes, NGF reduce...
متن کاملTherapeutic targeting of IL-6 trans signaling counteracts STAT3 control of experimental inflammatory arthritis.
Cytokine control of the synovial infiltrate is a central process in the development of inflammatory arthritis. In this study, we combine genetic approaches and intervention strategies to describe a fundamental requirement for IL-6-mediated STAT3 signaling in orchestrating the inflammatory infiltrate in monoarticular and systemic models of experimental arthritis. STAT3 activation via the common ...
متن کامل