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(American Journal of Pathology. 1999;154:623-632.)
© 1999 American Society for Investigative Pathology

Regular Articles

Interleukin-12 Is Synthesized by Mesangial Cells and Stimulates Platelet-Activating Factor Synthesis, Cytoskeletal Reorganization, and Cell Shape Change

Benedetta Bussolati*{dagger} , Filippo Mariano* , Luigi Biancone{ddagger} , Robert Foà{dagger}§ , Salvatore David{dagger} , Vincenzo Cambi{dagger} and Giovanni Camussi*{ddagger}

From the Laboratorio di Immunopatologia Renale,* Dipartimento di Medicina Interna, and Dipartimento di Scienze Biomediche ed Oncologia Umana,§ Università di Torino, the Cattedra di Nefrologia,{dagger} Università di Parma, and the Dipartimento di Scienze Cliniche e Biologiche,{ddagger} Università dell'Insubria, Italy

Preliminary studies indicate the involvement of interleukin (IL)-12 in experimental renal pathology. In the present study, we evaluated whether cultured glomerular mesangial cells are able to produce IL-12 and whether IL-12 may regulate some of their functions, including the cytoskeletal reorganization, the change in cell shape, and the production of platelet-activating factor (PAF). The results obtained indicate that pro-inflammatory stimuli, such as tumor necrosis factor-{alpha} and bacterial polysaccharides, induce the expression of IL-12 mRNA and the synthesis of the protein by cultured mesangial cells. Moreover, cultured mesangial cells were shown to bind IL-12 and to express the human low-affinity IL-12 ß1-chain receptor. When challenged with IL-12, mesangial cells produced PAF in a dose- and time-dependent manner and superoxide anions. No production of tumor necrosis factor-{alpha} and IL-8 was observed. Moreover, we demonstrate that IL-12 induced a delayed and sustained shape change of mesangial cells that reached its maximum between 90 and 120 minutes of incubation. The changes in cell shape occurred concomitantly with cytoskeletal rearrangements and may be consistent with cell contraction. As IL-12-dependent shape change of mesangial cells was concomitant with the synthesis of PAF, which is known to promote mesangial cell contraction, we investigated the role of PAF using two chemically different PAF receptor antagonists. Both antagonists inhibited almost completely the cell shape change induced by IL-12, whereas they were ineffective on angiotensin-II-induced cell shape change. In conclusion, our results suggest that mesangial cells can either produce IL-12 or be stimulated by this cytokine to synthesize PAF and to undergo shape changes compatible with cell contraction.




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