Innate immunity triggers IL-32 expression by fibroblast-like synoviocytes in rheumatoid arthritis.
Innate immunity triggers IL-32 expression by fibroblast-like synoviocytes in rheumatoid arthritis.
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DOI：
10.1186/ar3073
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发表时间：
2010
影响因子：
4.9
通讯作者：
Sibilia J
中科院分区：
文献类型：
--
作者：
Alsaleh G;Sparsa L;Chatelus E;Ehlinger M;Gottenberg JE;Wachsmann D;Sibilia J
白介素32(IL-32)是一种新近发现的细胞因子，是肿瘤坏死因子-α、IL-1β、IL-6和IL-8等促炎细胞因子的强烈诱导者。这种细胞因子在类风湿滑膜中的表达高度增加，并与关节炎症的严重程度相关。成纤维细胞样滑膜细胞(Fls)对IL-32的天然免疫调节作用知之甚少。因此，我们研究了Toll样受体(TLR2)、TLR3和TLR4的配体以及细胞因子如肿瘤坏死因子α和干扰素γ对FLSS表达IL-32的影响。根据ACR标准从类风湿性关节炎(RA)患者中分离出Fls。定量逆转录聚合酶链式反应、共聚焦分析和酶联免疫吸附试验检测TLR2(BLP)、TLR3(PolyI：C)和TLR4(脂多糖)配体、肿瘤坏死因子-α和干扰素-γ刺激的FLSS对IL-32mRNA的诱导和IL-32mRNA的释放。TLR2、-3和-4配体以及干扰素-γ和肿瘤坏死因子-α可诱导RA-FLSS诱导IL-32β，γ和δ的表达。成熟的IL-32在细胞内表达，并由不同激活剂刺激的细胞释放。IL-32α亚型在细胞内表达，对α和PolyI：C有反应，在培养上清液中不释放。与单独用干扰素-α刺激相比，肿瘤坏死因子-γ、脂多糖、脂多糖或多聚I：C联合干扰素-γ刺激FLS可增加IL-32的表达。在类风湿性关节炎中，IL-32的合成受到天然免疫的严格调控。因此，RA患者滑膜组织中高水平分泌的肿瘤坏死因子-α、干扰素-γ、双链核糖核酸、透明质酸或其他损伤相关分子模式(DAMP)可能会刺激Flss分泌IL-32。因此，IL-32可能是RA的一个相关治疗靶点。
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. 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. 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. 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.
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DOI：
10.1073/pnas.0712381105
发表时间：
2008-03-04
影响因子：
11.1
作者：
Netea, Mihai G.;Lewis, Eli C.;Kim, Soo-Hyun
通讯作者：
Kim, Soo-Hyun
类风湿关节炎中滑膜细胞。滑膜成纤维细胞。
影响因子：
4.9
作者：
Mueller-Ladner, Ulf;Ospelt, Caroline;Gay, Steffen;Distler, Oliver;Pap, Thomas
通讯作者：
Pap, Thomas
影响因子：
4.8
作者：
Ohmori, Y;Schreiber, RD;Hamilton, TA
通讯作者：
Hamilton, TA
影响因子：
--
作者：
Ospelt, Caroline;Brentano, Fabia;Kyburz, Diego
通讯作者：
Kyburz, Diego
影响因子：
--
作者：
Brentano, F;Schorr, O;Kyburz, D
通讯作者：
Kyburz, D