Differential effects of Sendai virus infection on mediator synthesis by mesangial cells from two mouse strains

Differential effects of Sendai virus infection on mediator syn- thesis by mesangial cells from two mouse strains. Background. Recently, we observed that the severity of glo- merulonephritis in an experimental model of immunoglobulin A nephropathy (IgAN) induced by Sendai virus differs be- tween C57BL/6 and BALB/c mouse strains. The determinants of differing renal insufficiency are not understood. In the pres- ent study, we examine the capacity for mesangial cells to sup- port Sendai viral replication and assess the direct effects of Sendai virus on the production of selected cytokines, chemo- kines, and eicosanoids by mesangial cells, comparing C57BL/6 to BALB/c mouse strains. Methods. Sendai virus replication was measured by viral plaque assay using LLCMK2 cells. Production of cytokines (interleukin-6 (IL-6) and tumor necrosis factor- (TNF-)), chemokines (JE and KC), and eicosanoids (prostaglandin E2 (PGE2) and thromboxane B2 (TxB2)) in culture medium was evaluated by sandwich enzyme-linked immunosorbent assay (ELISA) or competitive enzyme immunoassay (EIA) after 48 hours' incubation with infectious or inactivated Sendai virus. Results. Sendai virus replicates equally well in mesangial cells from both strains, and infection evokes increased IL-6, JE, KC, and PGE2 production in relation to viral dose. BALB/c mesangial cells produce significantly more IL-6 and JE than those from C57BL/6, and the dose response for KC is steeper in BALB/c mesangial cells than those from C57BL/6. Synthesis of PGE2 in BALB/c mesangial cells is higher than that of C57BL/6 mesangial cells, both under basal conditions and in response to infectious Sendai virus, again in a dose-dependent manner. There is no TNF- or thromboxane response to viral stimulation. Conclusion. We conclude that different mesangial cell re- sponses to this common mucosal viral pathogen might influence the severity of IgAN in our model system. Immunoglobulin A nephropathy (IgAN), the most common form of glomerulonephritis in the world, is a