Cell Mol Life Sci：科学家发现新的炎症治疗目标

称为初级纤毛的微小细胞器是抗击炎症的关键，伦敦玛丽大学的科学家们发现了一种新的抗击炎症的治疗目标。

相关研究论文发表在Cellular and Molecular Life Sciences杂志上，研究人员发现称为初级纤毛的微小细胞器对调节炎症反应很重要。这一发现可能为百万计患有关节炎的人带来潜在的新的治疗方法。

Martin Knight博士说：“虽然初级纤毛已经发现了有一个多世纪前，但我们才刚刚开始意识到它的重要性，它们在不同的疾病和条件下发挥潜在的治疗益处，可以操纵纤毛结构和功能。

研究人员研究了初级纤毛在炎症反应中的作用。他们把软骨细胞暴露于称为细胞因子特别是白细胞介素1（IL-1）的炎症蛋白环境下，看初级纤毛是否有任何变化。

他说：当我们暴露了细胞于IL-1时，初级纤毛长度在短短的三个小时内增加了50％。

但当我们处理细胞以防止这种纤毛的延伸时。软骨细胞的炎症蛋白大大降低了。研究人员表示：如果我们能更好地操纵初级纤毛，我们就可能会减弱甚至防止发炎。

doi:10.1007/s00018-012-0980-y
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Primary cilia elongation in response to interleukin-1 mediates the inflammatory response

A. K. T. Wann and M. M. Knight

Primary cilia are singular, cytoskeletal organelles present in the majority of mammalian cell types where they function as coordinating centres for mechanotransduction, Wnt and hedgehog signalling. The length of the primary cilium is proposed to modulate cilia function, governed in part by the activity of intraflagellar transport (IFT). In articular cartilage, primary cilia length is increased and hedgehog signaling activated in osteoarthritis (OA). Here, we examine primary cilia length with exposure to the quintessential inflammatory cytokine interleukin-1 (IL-1), which is up-regulated in OA. We then test the hypothesis that the cilium is involved in mediating the downstream inflammatory response. Primary chondrocytes treated with IL-1 exhibited a 50 % increase in cilia length after 3 h exposure. IL-1-induced cilia elongation was also observed in human fibroblasts. In chondrocytes, this elongation occurred via a protein kinase A (PKA)-dependent mechanism. G-protein coupled adenylate cyclase also regulated the length of chondrocyte primary cilia but not downstream of IL-1. Chondrocytes treated with IL-1 exhibit a characteristic increase in the release of the inflammatory chemokines, nitric oxide and prostaglandin E2. However, in cells with a mutation in IFT88 whereby the cilia structure is lost, this response to IL-1 was significantly attenuated and, in the case of nitric oxide, completely abolished. Inhibition of IL-1-induced cilia elongation by PKA inhibition also attenuated the chemokine response. These results suggest that cilia assembly regulates the response to inflammatory cytokines. Therefore, the cilia proteome may provide a novel therapeutic target for the treatment of inflammatory pathologies, including OA.