Angiotensin II stimulates interleukin-6 release from cultured mouse mesangial cells.
Interleukin-6 (IL-6) is a multifunctional cytokine exerting a wide variety of biologic responses, including cell proliferation. Recently, IL-6 has been known to play a role in the pathogenesis of mesangial proliferative glomerulonephritis. IL-6 is now recognized as an autocrine growth factor for glomerular mesangial cells, and various inflammatory mediators have been shown to promote IL-6 release from mesangial cells. However, little is known about the noninflammatory stimuli of IL-6 release from mesangial cells. In this study, it was hypothesized that angiotensin II (AngII) is one of the noninflammatory mediators of IL-6 release in mesangial cells, and the effects of AngII on IL-6 release and mRNA expression in cultured mouse mesangial cells (CMMC) were investigated. It was demonstrated that AngII (10(-7) M or higher) caused IL-6 release and mRNA accumulation in CMMC. IL-6 release was detected at 4 h and reached a plateau at 8 h after the addition of AngII, whereas IL-6 mRNA expression peaked at 4 h. The effects of AngII on IL-6 release and gene expression were completely blocked by the AngII receptor type 1 (AT1 receptor) antagonist CV-11974. AngII and IL-6 were both shown to stimulate DNA synthesis in CMMC, and the blockade of IL-6 signaling with anti-IL-6 receptor antibody abolished the enhanced DNA synthesis induced by AngII. These results raise a possibility that the growth-promoting effect of AngII on mesangial cells is at least partially mediated by IL-6 released from mesangial cells.
Moriyama
T
T
First Department of Medicine, Osaka University School of Medicine, Japan.
Fujibayashi
M
M
Fujiwara
Y
Y
Kaneko
T
T
Xia
C
C
Imai
E
E
Kamada
T
T
Ando
A
A
Ueda
N
N
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D015432:Glomerulonephritis, Membranoproliferative / Q000209:etiology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D007700:Kinetics; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D015850:Interleukin-6; D012333:RNA, Messenger; D013777:Tetrazoles; D000804:Angiotensin II; D004247:DNA; C081643:candesartan