%0 Journal Article
%T Innate immunity triggers IL-32 expression by fibroblast-like synoviocytes in rheumatoid arthritis
%A Ghada Alsaleh
%A Laetitia Sparsa
%A Emmanuel Chatelus
%A Mathieu Ehlinger
%A Jacques-Eric Gottenberg
%A Dominique Wachsmann
%A Jean Sibilia
%J Arthritis Research & Therapy
%D 2010
%I BioMed Central
%R 10.1186/ar3073
%X FLSs were isolated from patients with rheumatoid arthritis (RA) according to the ACR criteria. Quantitative RT-PCR, confocal analysis, and ELISA were performed to evaluate IL-32 mRNA induction and IL-32 release by FLSs stimulated with TLR2 (BLP), TLR3 (poly I:C), and TLR4 (lipopolysaccharide) ligands, TNF-¦Á and IFN-¦Ã.TLR2, -3, and -4 ligands as well as IFN-¦Ã and TNF-¦Á induced IL-32 ¦Â, ¦Ã and ¦Ä mRNA expression by RA FLSs. Mature IL-32 was expressed intracellularly and released by cells stimulated with the various activators. The IL-32¦Á isoform was expressed intracellularly in response to TNF-¦Á and poly I:C and not released in culture supernatants. Stimulation of FLS with TNF-¦Á, BLP, lipopolysaccharide, or poly I:C concomitant with IFN-¦Ã increased IL-32 expression compared with stimulation with IFN-¦Ã alone.IL-32 synthesis by FLSs is tightly regulated by innate immunity in rheumatoid arthritis. Thus TNF-¦Á, IFN-¦Ã, double-strand RNA, hyaluronic acid, or other damage-associated molecular patterns (DAMPs), highly secreted in synovial tissues of RA patients, might trigger IL-32 secretion by FLSs. IL-32 might therefore represent a relevant therapeutic target in RA.Rheumatoid arthritis (RA) is a systemic inflammatory disease that affects predominantly multiple peripheral joints. Although the exact mechanisms that contribute to the pathogenesis are still largely unknown, it is well accepted that numerous inflammatory cells such as T and B cells, fibroblast-like synoviocytes, antigen-presenting cells, and their extensive production of proinflammatory mediators such as TNF-¦Á, IL-1, IL-6, IL-15, IL-17, and IL-18, are implicated [1].IL-32, a recently described cytokine produced mainly by NK cells, T lymphocytes, epithelial cells, and blood monocytes stimulated by IL-2 or IFN-¦Ã, has recently emerged as an important player in innate immune responses [2,3]. This proinflammatory cytokine is a strong inducer of other proinflammatory cytokines such as TNF-¦Á, IL-1¦Â, IL-6, IL-8, and macrop
%U http://arthritis-research.com/content/12/4/R135