Cytokine-induced expression of leukemia inhibitory factor in renal mesangial cells

Abstract

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.

Leukemia Inhibitory Factor Is Involved in Tubular Regeneration after Experimental Acute Renal Failure

“…LIF has been identified within the urine of renal allograft recipients during episodes of acute rejection (24). The LIF expression level in cultured mesangial cells has been shown to be increased by cytokines (25). Glomerulonephritis induces LIF in the glomeruli, and administration of exogenous LIF ameliorates glomerulonephritis (26).…”

Upregulation of chemokine (C–C motif) ligand 20 in adult epidermal keratinocytes in direct current electric fields

“…TNF- α may also be responsible for increased expression of CCL20, which functions to recruit inflammatory cells to tissue and has been found to be expressed in epidermal cells with disrupted barrier function and therefore in the presence of EFs [13, 27, 41]. Increased expression of cytokines and chemokines may also result in the upregulation of leukemia inhibitory factor (LIF), which then may reinforce upregulation of cytokines, particularly interleukins [14, 48]. …”

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“…On the other hand, and in contrast with mesangial cells [9], liver myofibroblasts do not appear to express cell surface LIF-specific gp190 receptor subunit. This is based on results obtained from immunohistochemistry, flow cytometry, as well as functional experiments.…”