Witowski J, Pawlaczyk K, Breborowicz A, Scheuren A, Kuzlan-Pawlaczyk M, Wisniewska J, Polubinska A, Friess H, Gahl G M, Frei U, Jörres A
Department of Pathophysiology, University Medical School, Poznan, Poland.
J Immunol. 2000 Nov 15;165(10):5814-21. doi: 10.4049/jimmunol.165.10.5814.
IL-17 is a newly discovered cytokine implicated in the regulation of hemopoiesis and inflammation. Because IL-17 production is restricted to activated T lymphocytes, the effects exerted by IL-17 may help one to understand the contribution of T cells to the inflammatory response. We investigated the role of IL-17 in leukocyte recruitment into the peritoneal cavity. Leukocyte infiltration in vivo was assessed in BALB/Cj mice. Effects of IL-17 on chemokine generation in vitro were examined in human peritoneal mesothelial cells (HPMC). Administration of IL-17 i.p. resulted in a selective recruitment of neutrophils into the peritoneum and increased levels of KC chemokine (murine homologue of human growth-related oncogene alpha (GROalpha). Pretreatment with anti-KC Ab significantly reduced the IL-17-driven neutrophil accumulation. Primary cultures of HPMC expressed IL-17 receptor mRNA. Exposure of HPMC to IL-17 led to a dose- and time-dependent induction of GROalpha mRNA and protein. Combination of IL-17 together with TNF-alpha resulted in an increased stability of GROalpha mRNA and synergistic release of GROalpha protein. Anti-IL-17 Ab blocked the effects of IL-17 in vitro and in vivo. IL-17 is capable of selectively recruiting neutrophils into the peritoneal cavity via the release of neutrophil-specific chemokines from the peritoneal mesothelium.
白细胞介素-17是一种新发现的细胞因子，参与造血和炎症调节。由于白细胞介素-17的产生仅限于活化的T淋巴细胞，因此白细胞介素-17所发挥的作用可能有助于人们了解T细胞在炎症反应中的作用。我们研究了白细胞介素-17在白细胞募集到腹腔中的作用。在BALB/Cj小鼠体内评估白细胞浸润情况。在人腹膜间皮细胞（HPMC）中检测白细胞介素-17对体外趋化因子生成的影响。腹腔注射白细胞介素-17导致中性粒细胞选择性募集到腹膜，并使KC趋化因子（人类生长相关癌基因α（GROα）的小鼠同源物）水平升高。用抗KC抗体预处理可显著减少白细胞介素-17驱动的中性粒细胞聚集。HPMC原代培养物表达白细胞介素-17受体mRNA。将HPMC暴露于白细胞介素-17会导致GROα mRNA和蛋白质呈剂量和时间依赖性诱导。白细胞介素-17与肿瘤坏死因子-α联合使用可导致GROα mRNA稳定性增加和GROα蛋白质协同释放。抗白细胞介素-17抗体在体外和体内均阻断了白细胞介素-17的作用。白细胞介素-17能够通过从腹膜间皮释放中性粒细胞特异性趋化因子，选择性地将中性粒细胞募集到腹腔。
