| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Alsaleh, Ghada Sparsa, Laetitia Chatelus, Emmanuel Ehlinger, Mathieu Gottenberg, Jacques-Eric Wachsmann, Dominique Sibilia, Jean |
| Abstract | Introduction Interleukin-32 (IL-32) is a recently described cytokine that is a strong inducer of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, IL-1β, IL-6, and IL-8. The expression of this cytokine is highly increased in the rheumatoid synovium and correlated with the severity of joint inflammation. Little is known regarding the innate immune-related regulation of IL-32 by fibroblast-like synoviocytes (FLSs). We therefore investigated the effect of innate immune stimulation by ligands of Toll-like receptor (TLR)2, TLR3, and TLR4, and cytokines such as TNF-α and interferon (IFN)-γ, on IL-32 expression by FLSs. Methods 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-α and IFN-γ. Results TLR2, -3, and -4 ligands as well as IFN-γ and TNF-α induced IL-32 β, γ and δ mRNA expression by RA FLSs. Mature IL-32 was expressed intracellularly and released by cells stimulated with the various activators. The IL-32α isoform was expressed intracellularly in response to TNF-α and poly I:C and not released in culture supernatants. Stimulation of FLS with TNF-α, BLP, lipopolysaccharide, or poly I:C concomitant with IFN-γ increased IL-32 expression compared with stimulation with IFN-γ alone. Conclusions IL-32 synthesis by FLSs is tightly regulated by innate immunity in rheumatoid arthritis. Thus TNF-α, IFN-γ, 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. |
| Related Links | https://arthritis-research.biomedcentral.com/counter/pdf/10.1186/ar3073.pdf |
| Ending Page | 11 |
| Page Count | 11 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14786362 |
| DOI | 10.1186/ar3073 |
| Journal | Arthritis Research & Therapy |
| Issue Number | 4 |
| Volume Number | 12 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2010-07-08 |
| Access Restriction | Open |
| Subject Keyword | Rheumatology Orthopedics Rheumatoid Arthritis Rheumatoid Arthritis FLSs Concomitant Stimulation Relevant Therapeutic Target Innate Immune Stimulation |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology Rheumatology |
| Journal Impact Factor | 4.4/2023 |
| 5-Year Journal Impact Factor | 4.9/2023 |
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