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

Isabella Coletta, Lucia Soldo, Nadia Polentarutti, Francesca Mancini, Angelo Guglielmotti, Mario Pinza, Alberto Mantovani, Claudio Milanese

Research output: Contribution to journalArticlepeer-review

Abstract

Interleukin (IL) 6, an autocrine growth factor for mesangial cells, and chemokines, which are released from activated mesangial cells and induce leukocyte infiltration, play a critical role in the progression of immune system mediated renal diseases. Since the reciprocal relationship between IL- 6 and chemokines in renal inflammation has been barely investigated, we have analyzed whether IL-6 (500 ng/ml), alone or in combination with the soluble form 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 chemoattractant protein 1), IL-8, Rantes (regulated on activation, normal T cell expressed and secreted), and MIP-1α (macrophage inflammatory protein 1α. Whereas IL-6 or sIL-6R alone were ineffective in inducing significant chemokine release from NHMC, the simultaneous treatment with IL6 and sIL-6R showed a significant interaction, leading to a strong synergic effect on MCP- 1 synthesis and release without exerting any relevant activity on IL-8, Rantes, or MIP-1α. Consistently with the unresponsiveness to IL-6, mRNA and protein expression analysis of the two subunits which form the functional IL- 6 receptor showed that NHMC express only the gp130 signal-transducing chain and not the subunit-specific IL-6R (gp80). These findings support an unexpected role of the IL-6 system in kidney inflammatory reactions through the selective regulation of monocyte recruitment.

Original languageEnglish
Pages (from-to)37-43
Number of pages7
JournalExperimental Nephrology
Volume8
Issue number1
Publication statusPublished - Jan 2000

Keywords

  • Chemokines
  • Interleukin 6
  • Interleukin 6 receptor
  • MCP-1
  • Mesangial cells

ASJC Scopus subject areas

  • Nephrology

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