Lymphocyte-derived cytokines induce sequential expression of monocyte- and T cell-specific chemokines in human mesangial cells.

Chemokines are a family of small related proteins that play an important role in the selective recruitment of different leukocyte populations to the sites of inflammation. Human glomerular mesangial cells are potent producers of a variety of chemokines. Here we examined the kinetics of mesangial cell chemokine expression with focus on the C-C or beta chemokines monocyte chemoattractant protein-1 (MCP-1), regulated upon activation, normal T cell expressed and secreted (RANTES), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and the C-X-C or alpha chemokine interleukin-8 (IL-8) in response to lymphocyte- or monocyte-derived cytokines and mesangial cell growth factors. It was found that interferon-gamma (IFN-gamma), a cytokine produced by TH1 lymphocytes, synergized with tumor necrosis factor-alpha (TNF-alpha) in RANTES expression and with IL-1 beta in MCP-1 synthesis. Time course studies revealed an early peak of mRNA expression of monocyte-specific MCP-1 upon activation with TNF-alpha in contrast to T cell-specific RANTES, which reached the highest mRNA level after 18 hours. This sequence of TNF-alpha-induced MCP-1 and RANTES expression was confirmed on the protein level. As another T-lymphocyte specific chemokine, MIP-1 alpha mRNA and protein was expressed only in response to TNF-alpha plus IFN-gamma with kinetics similar to those of RANTES expression. Finally, unlike other mesangial growth factors basic fibroblast growth factor (bFGF) induced MCP-1, RANTES, and IL-8 mRNA expression, suggesting an involvement of autocrine regulation mechanisms in mesangial chemokine expression.