Interleukin 6 is an autocrine growth factor for mesangial cells

Abstract

Interleukin 6 (IL-6) induces the acute phase response, differentiation of B cells, proliferation of T cells, thymocytes, hematopoietic progenitors, hybridoma and plasmacytoma cells. Monocytes, T cells, fibroblasts, epithelial and endothelial cells secrete IL-6. Since IL-6 responsive cell-types may participate in the pathogenesis of glomerular inflammation, we studied the secretion of IL-6 by rat MCs, using the IL-6 dependent hybridoma cell line B9. The results of our studies indicate that MCs secrete IL-6 with a molecular weight of 17-42 kDa and isoelectric point of 4.0 to 5.3 MC-IL-6 activity could be blocked by a polyclonal antimurine-IL-6 antibody. MC express IL-6 mRNA as determined by Northern blot. Furthermore, our data demonstrate that IL-6 acts as an autocrine growth factor for MC. Incubation of subconfluent MC with recombinant IL-6 results in a dose-dependent increase of 3H-thymidine incorporation and number of MCs. Moreover, reverse phase HPLC fractions of MC-CM containing IL-6 activity increase 3H-thymidine incorporation by MC. In addition to its possible paracrine role in mediating the immune response in the glomerulus, MC-IL-6 may also be one of the autocrine signals leading to mesangial cell proliferation in vivo.

Correlation of tumor necrosis factor alpha and interleukin 6 with hypertensive renal damage

“…27 Furthermore, IL-6 and TNF-a can also induce the contraction and proliferation of mesangial cells, [28][29][30] deposit of matrix, acceleration of glomerulosclerosis, and stimulate the proliferation of the fibroblast, whereby to produce collagen fibers which can finally lead to renal fibrosis.…”

Inhibition of Interleukin-10 by the Immunomodulator AS101 Reduces Mesangial Cell Proliferation in Experimental Mesangioproliferative Glomerulonephritis

“…Excessive proliferation of mesangial cells is usually associated with matrix expansion, leading to the development of glomerular sclerosis (2). Mesangial cells proliferate in response to a variety of growth factors and cytokines such as platelet-derived growth factor (PDGF), basic fibroblast growth factor, and interleukin-6 (3)(4)(5). Recently, we showed that IL-10 is a potent mesangial autocrine growth factor that plays a pivotal role in rat MC proliferation in vitro (6).…”

Suppression of Experimental Crescentic-Type Anti-Glomerular Basement Membrane (GBM) Nephritis by FK506 (Tacrolimus Hydrate) in Rats

“…It has been reported that IL-6 transgenic mouse excretes urinary protein, causing the progression of mesangial proliferative glomerulonephritis (41). Moreover, in both in vivo and in vitro studies, recombinant IL-6 induced the growth of rat mesangial cells (42)(43)(44). These findings suggest that the suppressed glomerular cell proliferation by FK506 is due to the inhibition of IL-6 through the inhibition of IL-2 production.…”