Hartner A, Goppelt-Struebe M, Hocke G M, Sterzel R B
Medizinische Klinik IV, Universitaet Erlangen-Nuernberg, Germany.
Kidney Int. 1997 Jun;51(6):1754-60. doi: 10.1038/ki.1997.241.
M. Leukemia inhibitory factor (LIF). oncostatin M (OsM) and interleukin-6 (IL-6) are members of a cytokine family, which are produced by activated macrophages and glomerular mesangial cells. These cytokines have been implicated in the pathogenesis of glomerular inflammation, but their action on glomerular cells is presently unclear. Therefore, we examined the effects of IL-6, OsM and LIF on chemokine synthesis of rat mesangial cells in culture. While LIF as well as IL-6 up-regulated monocyte chemotactic protein-1 (MCP-1) mRNA expression, OsM showed no such effect. The induction of MCP-1 mRNA by LIF and IL-6 was transient, peaking at one to two hours and two to three hours, respectively, and returning to background levels within several hours. Induction of MCP-1 mRNA by LIF and IL-6 was strongly inhibited by dexamethasone. LIF activated STAT factors in mesangial cells, suggesting their involvement in signal transduction pathways that lead to LIF-stimulated up-regulation of MCP-1 mRNA. By contrast, LIF. IL-6 and OsM failed to affect the expression of the chemokines, macrophage inflammatory protein-2 (MIP-2) and RANTES. The rapid, transient and differential regulation of MCP-1 expression induced by LIF and IL-6 contrasted with uniformly powerful effects of the proinflammatory cytokines IL-1 beta and TNF alpha that induced all tested chemokines for prolonged time periods. These results suggest that the selective and transient induction of MCP-1 by LIF and IL-6 may play a role in the preferential attraction of monocytes to the injured glomerulus.
M.白血病抑制因子（LIF）、制瘤素M（OsM）和白细胞介素-6（IL-6）是细胞因子家族的成员，由活化的巨噬细胞和肾小球系膜细胞产生。这些细胞因子与肾小球炎症的发病机制有关，但其对肾小球细胞的作用目前尚不清楚。因此，我们研究了IL-6、OsM和LIF对培养的大鼠系膜细胞趋化因子合成的影响。LIF和IL-6均可上调单核细胞趋化蛋白-1（MCP-1）mRNA的表达，而OsM则无此作用。LIF和IL-6对MCP-1 mRNA的诱导是短暂的，分别在1至2小时和2至3小时达到峰值，并在数小时内恢复到背景水平。地塞米松强烈抑制LIF和IL-6对MCP-1 mRNA的诱导。LIF激活系膜细胞中的信号转导和转录激活因子（STAT），提示其参与导致LIF刺激MCP-1 mRNA上调的信号转导途径。相比之下，LIF、IL-6和OsM未能影响趋化因子巨噬细胞炎性蛋白-2（MIP-2）和调节激活正常T细胞表达和分泌的趋化因子（RANTES）的表达。LIF和IL-6对MCP-1表达的快速、短暂和差异性调节与促炎细胞因子IL-1β和肿瘤坏死因子α（TNFα）的持续强效作用形成对比，IL-1β和TNFα可长时间诱导所有检测的趋化因子。这些结果表明，LIF和IL-6对MCP-1的选择性和短暂诱导可能在单核细胞向受损肾小球的优先趋化中起作用。
