In vitro effects of interleukins on human mesangial cells: implications for glomerulonephritis.
Intrinsic glomerular cells, especially mesangial cells, are considered to be actively involved in the pathogenesis of glomerulonephritis (GN), but the precise mechanism(s) remains elusive. We have previously demonstrated that nephritogenic IgA immune complex can stimulate human mesangial cells (HMCs) to increase their production of interleukin-1 (IL-1) and interleukin-6 (IL-6). In order to evaluate the roles of cytokines such as IL-1 and/or IL-6 and mesangial cells as mediators of renal injury in GN, we have now examined the changes of HMCs and their secreted products in vitro, after stimulation with various concentrations of IL-1 and IL-6. Cytokine-activated HMCs showed the following changes: (1) increased cell size, with intracytoplasmic vacuoles, dilated endoplasmic reticulum, increased free ribosomes and polysomes, and mitochondrial swelling; (2) increased cell proliferation, reflected in thymidine incorporation and an increased proportion of S and G2/M phase cells by cell cycle analysis; (3) enhancement of IL-6 mRNA expression in HMCs with stimulation of IL-6 alone or IL-1 plus IL-6; and (4) release of large amounts of platelet activating factor (PAF), thromboxane B2 (TxB2), and superoxide anion. Taken together, these results strongly suggest that mesangial cell proliferation and increased production of immune/chemical mediators and superoxide anion can be directly induced by IL-1 plus IL-6. These changes may lead to ongoing renal injury.
Chen
W P
WP
Department of Pediatrics, Veterans General Hospital-Taipei, Taiwan, Republic of China.
Chen
A
A
Lin
C Y
CY
D000293:Adolescent; D000328:Adult; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005921:Glomerulonephritis / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000378:metabolism; D013268:Stimulation, Chemical; D013481:Superoxides / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D010972:Platelet Activating Factor; D013481:Superoxides; D013929:Thromboxane B2