CYTOKINE-INDUCED EXPRESSION OF LEUKEMIA INHIBITORY FACTOR IN RENAL MESANGIAL CELLS

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine, which shar es many characteristics with interleukin-6 (IL-6). Recent observations indicate a role for LIF in inflammatory processes. To examine the pot ential 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 exogen ous 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 c ytokines, 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). Th e induction was transient with a peak after three to five hours. Dexam ethasone (0.1 mu M) almost completely inhibited the induction of LIF. Weak induction of LIF mRNA was observed after stimulation with basic f ibroblast growth factor, endothelin and transforming growth factor bet a. 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 express ion. A similar induction pattern was observed for the expression of IL -6 mRNA. LIF protein was detected by specific ELISA in the supernatant s of human mesangial cells stimulated with LPS or IL-IP. In addition, we found that mesangial cells not only express LIF but they are also t arget cells for LIF. Recombinant LIF effectively induced transient exp ression of the immediate early genes, c-fos, jun-B and Egr-1 in rat me sangial cells, with a maximum at 30 to 60 minutes. LIF was not mitogen ic for mesangial cells. Our findings indicate that glomerular mesangia l cells produce and react to LIF. As a cytokine with autocrine potenti al, LIF may play a physiological and/or pathophysiological role in the glomerulus, the exact nature and relevance of which remain to be expl ored.