Hartner A, Sterzel R B, Reindl N, Hocke G M, Fey G H, Goppelt-Struebe M
Medizinische Klinik IV, Universitaet Erlangen-Nuernberg, Germany.
Kidney Int. 1994 Jun;45(6):1562-71. doi: 10.1038/ki.1994.206.
Leukemia inhibitory factor (LIF) is a pleiotropic cytokine, which shares many characteristics with interleukin-6 (IL-6). Recent observations indicate a role for LIF in inflammatory processes. To examine the potential involvement of LIF in the regulation of mesangial cell behavior, we studied LIF expression in early primary cultures of rat and human mesangial cells, as well as the response of mesangial cells to exogenous LIF. Growing or growth-arrested rat mesangial cells constitutively expressed very low levels of LIF mRNA, barely detectable by Northern blot analysis. Strong induction of LIF mRNA expression was caused by cytokines, such as interleukin-1 beta (5 ng/ml), tumor necrosis factor alpha (100 ng/ml) and PDGF (100 ng/ml), as well as LPS (200 ng/ml). The induction was transient with a peak after three to five hours. Dexamethasone (0.1 microM) almost completely inhibited the induction of LIF. Weak induction of LIF mRNA was observed after stimulation with basic fibroblast growth factor, endothelin and transforming growth factor beta. In combination with IL-1 beta, TGF beta showed synergistic effects on LIF induction. LIF itself or IL-6 had no effect on LIF mRNA expression. A similar induction pattern was observed for the expression of IL-6 mRNA. LIF protein was detected by specific ELISA in the supernatants of human mesangial cells stimulated by LPS or IL-1 beta. In addition, we found that mesangial cells not only express LIF but they are also target cells for LIF. Recombinant LIF effectively induced transient expression of the immediate early genes, c-fos, jun-B and Egr-1 in rat mesangial cells, with a maximum at 30 to 60 minutes. LIF was not mitogenic for mesangial cells. Our findings indicate that glomerular mesangial cells produce and react to LIF. As a cytokine with autocrine potential, LIF may play a physiological and/or pathophysiological role in the glomerulus, the exact nature and relevance of which remain to be explored.
白血病抑制因子（LIF）是一种多效性细胞因子，与白细胞介素-6（IL-6）具有许多共同特征。最近的观察表明LIF在炎症过程中发挥作用。为了研究LIF在系膜细胞行为调节中的潜在作用，我们研究了大鼠和人系膜细胞原代早期培养物中LIF的表达，以及系膜细胞对外源LIF的反应。生长或生长停滞的大鼠系膜细胞组成性表达极低水平的LIF mRNA，通过Northern印迹分析几乎检测不到。细胞因子如白细胞介素-1β（5 ng/ml）、肿瘤坏死因子α（100 ng/ml）和血小板衍生生长因子（100 ng/ml）以及脂多糖（200 ng/ml）可强烈诱导LIF mRNA表达。诱导是短暂的，在三到五小时后达到峰值。地塞米松（0.1 microM）几乎完全抑制LIF的诱导。在用碱性成纤维细胞生长因子、内皮素和转化生长因子β刺激后，观察到LIF mRNA的弱诱导。与IL-1β联合使用时，TGFβ对LIF诱导具有协同作用。LIF本身或IL-6对LIF mRNA表达没有影响。IL-6 mRNA的表达也观察到类似的诱导模式。通过特异性ELISA在脂多糖或IL-1β刺激的人系膜细胞上清液中检测到LIF蛋白。此外，我们发现系膜细胞不仅表达LIF，而且它们也是LIF的靶细胞。重组LIF有效诱导大鼠系膜细胞中即刻早期基因c-fos、jun-B和Egr-1的瞬时表达，在30至60分钟时达到最大值。LIF对系膜细胞没有促有丝分裂作用。我们的研究结果表明肾小球系膜细胞产生LIF并对其作出反应。作为一种具有自分泌潜力的细胞因子，LIF可能在肾小球中发挥生理和/或病理生理作用，其确切性质和相关性仍有待探索。
