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首页> 外文期刊>Clinical and Experimental Immunology: An Official Journal of the British Society for Immunology >The effects of interleukin-18 on rat articular chondrocytes: a study of mRNA expression and protein synthesis of proinflammatory substances.
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The effects of interleukin-18 on rat articular chondrocytes: a study of mRNA expression and protein synthesis of proinflammatory substances.

机译：白细胞介素18对大鼠关节软骨细胞的影响：促炎物质mRNA表达和蛋白质合成的研究。

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摘要

Interleukin (IL)-18 is a potent stimulator of immunity and augments the severity of type II collagen-induced arthritis (CIA) in rats and mice by enhancing T helper 1 (Th1) cell activation, which increases the production of proinflammatory cytokines and arthritogenic antibodies. In this study, we show that recombinant IL-18 (rIL-18) also has a direct effect on normal rat chondrocytes maintained in vitro inducing them to produce proinflammatory factors including IL-6, regulated upon activation normal T cell expressed and secreted (RANTES), prostaglandin E(2) (PGE(2)) and prostaglandin F(2alpha) (PGF(2alpha)) in a dose- and time-dependent manner. The production of matrix metalloproteinase (MMP)-13, nitric oxide (NO), tumour necrosis factor (TNF)-alpha and IL-1beta were also enhanced, although less intensely. Neutralizing polyclonal anti-rIL-18 antibodies effectively blocked the production of IL-6, PGE(2) and RANTES, as well as mRNA expression for the same products in addition to IL-18 and TNF-alpha. In contrast, neutralizing antibodies to IL-1beta, TNF-alpha and IL-6 were ineffective in suppressing any of these products. Together, these findings suggest that IL-18 may play an important, possibly direct, role in mediating cartilage injury, which might not be amenable to treatment with currently utilized anti-cytokine agents. These findings suggest further that IL-18 antagonists might prove beneficial as anti-inflammatory and chondroprotective agents in the treatment of arthritis, and that the development of such agents for human use is worth consideration.
机译：白介素（IL）-18是一种有效的免疫刺激剂，可通过增强T辅助1（Th1）细胞活化来增强大鼠和小鼠II型胶原诱导的关节炎（CIA）的严重性，从而增加促炎性细胞因子和关节炎的产生抗体。在这项研究中，我们显示重组IL-18（rIL-18）对体外维持的正常大鼠软骨细胞也具有直接作用，诱导它们产生促炎因子，包括IL-6，在激活正常T细胞表达和分泌后对其进行调节（RANTES ），前列腺素E（2）（PGE（2））和前列腺素F（2alpha）（PGF（2alpha））呈剂量和时间依赖性。基质金属蛋白酶（MMP）-13，一氧化氮（NO），肿瘤坏死因子（TNF）-α和IL-1beta的产生也有所增强，尽管强度较弱。中和多克隆抗rIL-18抗体可有效阻断IL-6，PGE（2）和RANTES的产生，以及IL-18和TNF-α以外的相同产品的mRNA表达。相反，针对IL-1β，TNF-α和IL-6的中和抗体在抑制任何这些产物方面均无效。这些发现共同表明，IL-18可能在介导软骨损伤中起重要的作用，可能是直接的作用，而软骨损伤可能不适用于目前使用的抗细胞因子药物。这些发现进一步表明，IL-18拮抗剂可能被证明在关节炎的治疗中作为抗炎和软骨保护剂是有益的，并且值得人们考虑开发这种药物以供人类使用。

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