Selective Induction of MCP-1 in Human Mesangial Cells by the IL-6/sIL-6R Complex

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 IL-6 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.

The IL-6-Soluble IL-6Rα Autocrine Loop of Endothelial Activation as an Intermediate Between Acute and Chronic Inflammation: an Experimental Model Involving Thrombin

“…A similar observation has recently been made in mesangial cell lines (41). This may be an important point in vivo, because the pro-vs anti-inflammatory functions of IL-6 are still discussed.…”

Gp130 Signaling Promotes Development of Acute Experimental Colitis by Facilitating Early Neutrophil/Macrophage Recruitment and Activation

“…These observations suggested that besides myeloid cells also gp130-dependent signals in parenchymal cells were involved in controlling disease activity in the DSS model. The transcription of many chemokines and adhesion molecules is known to be P-STAT3 dependent in these cells (15,27). Using bone marrow chimeric mice, we could demonstrate that the influx of gp130 f/f leukocytes was significantly reduced in gp130-deficient recipient mice, which indicated a requirement for gp130 in non-bone marrow derived cells for mucosal inflammatory cell recruitment.…”

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

“…26 TNF-a can contribute to influence the coagulation system and fibrinolytic system by a variety of mechanisms including inducing the platelet to aggregate on the endothelial to form thrombi, inducing the mesangial cells to produce active substance similar to tissue factor, and increasing the activity of preclotting substances.…”