Interleukin-12 is synthesized by mesangial cells and stimulates platelet-activating factor synthesis, cytoskeletal reorganization, and cell shape change

Preliminary studies indicate the involvement of interleukin (IL)-12 in expe rimental renal pathology. In the present study, we evaluated whether cultur ed glomer ular mesangial cells are able to produce IL-12 and whether IL-12 may regulate some of their functions, including the cytoskeletal reorganiza tion, the change in cell shape, and the production of platelet-activating f actor (PAF). The results obtained indicate that pro-inflammatory stimuli, s uch as tumor necrosis factor-alpha and bacterial polysaccharides, induce th e expression of IL-12 mRNA and the synthesis of the protein by cultured mes angial cells. Moreover, cultured mesangial cells were shown to bind IL-12 a nd to express the human low-affinity IL-12 beta 1-chain receptor. When chal lenged with IL-12, mesangial cells produced PAF in a dose- and time-depende nt manner and superoxide anions, No production of tumor necrosis factor-alp ha and IL-8 was observed. Moreover, me demonstrate that IL-12 induced a del ayed and sustained shape change of mesangial cells that reached its maximum between 90 and 120 minutes of incubation. The changes in cell shape occurr ed concomitantly with cytoskeletal rearrangements and may be consistent wit h 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 diff erent PAF receptor antagonists. Both antagonists inhibited almost completel y the cell shape change induced by IL-12, whereas they were ineffective on angiotensin-II-induced cell shape change. In conclusion, our results sugges t that mesangial cells can either produce IL-12 or be stimulated by this cy tokine to synthesize PAF and to undergo shape changes compatible with cell contraction.