Angiotensin II Enhances Interleukin-1 β-Induced MMP-9 Secretion in Adult Rat Cardiac Fibroblasts

[摘要] References(22)Cited-By(6)Cardiac fibroblasts play important roles during the cardiac remodeling through the secretion of matrix metalloproteinase (MMP)-9. Inflammatory cytokine, interleukin (IL)-1β induces MMP-9 secretion in cultured cardiac fibroblasts. Angiotensin II is well known to play pivotal roles in cardiac remodeling, but the effect of angiotensin II on MMP-9 secretion in cardiac fibroblasts has not been fully clarified. In the present study, we investigated the effect of angiotensin II on basal and IL-1β-induced MMP-9 secretion in adult rat cardiac fibroblasts. MMP-9 protein secreted into culture medium, and phosphorylation of nuclear factor (NF)-κB, c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in cell lysates were measured by Western blotting. Angiotensin II (1 nM, 24 hr) alone-treatment did not induce MMP-9 secretion. However, angiotensin II significantly enhanced IL-1β (4 ng/ml, 24 hr)-induced MMP-9 secretion. Telmisartan (10 nM), an angiotensin II type 1 receptor (AT1R) antagonist, significantly suppressed the enhancement of IL-1β-induced MMP-9 secretion by angiotensin II, whereas PD123319 (10 nM), an angiotensin II type 2 receptor antagonist, was ineffective. IL-1β (4 ng/ml, 10 min) induced phosphorylation of NF-κB, JNK, and ERK. Angiotensin II augmented the IL-1β-induced phosphorylation of ERK but not NF-κB and JNK. PD98059 (50 μM), a selective inhibitor of ERK pathway, inhibited the angiotensin II enhancement of IL-1β-induced MMP-9 secretion. These results suggest that angiotensin II enhances IL-1β-induced MMP-9 secretion through the augmentation of ERK phosphorylation via AT1R in adult rat cardiac fibroblasts.

[学科分类] 兽医学

[关键词] angiotensin II;cardiac fibroblasts;extracellular signal-regulated kinase;interleukin-1β;matrix metalloproteinase