Selective induction of MCP-1 in human mesangial cells by the IL-6/sIL-6R complex

Interleukin (IL) 6, an autocrine growth factor for mesangial cells, and che mokines, which are released from activated mesangial cells and induce leuko cyte infiltration, play a critical role in the progression of immune system mediated renal diseases. Since the reciprocal relationship between IL-6 an d chemokines in renal inflammation has been barely investigated, we have an alyzed whether IL-6 (500 ng/ml), alone or in combination with the soluble f orm of its receptor (sIL-6R, 200 ng/ml), can induce normal human mesangial cells (NHMC) to release alpha and/or beta chemokines: MCP-1 (monocyte chemo attractant protein 1), IL-8, Rantes (regulated on activation, normal T cell expressed and secreted), and MIP-1 alpha (macrophage inflammatory protein 1 alpha). Whereas IL-6 or sIL-6R alone were ineffective in inducing signifi cant chemokine release from NHMC, the simultaneous treatment with IL-6 and sIL-6R showed a significant interaction, leading to a strong synergic effec t on MCP-1 synthesis and release without exerting any relevant activity on IL-8, Rantes, or MIP-1 alpha. Consistently with the unresponsiveness to IL- 6, mRNA and protein expression analysis of the two sub-units which form the functional IL-6 receptor showed that NHMC express only the gp130 signal-tr ansducing chain and not the subunit-specific IL-6R (gp80). These findings s upport an unexpected role of the IL-6 system in kidney inflammatory reactio ns through the selective regulation of monocyte recruitment. Copyright (C) 2000 S. Karger AG, Basel.