Potentiated macrophage activation by acid sensing under low adiponectin levels

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• 作者：Takaharu Negoro ; Masaoki Kin ; Akitoshi Takuma ; Kiyomi Saito ; Shunichi Shimizu ; Yasuko Nakano
• 关键词：Adiponectin ; Acid-sensing ion channels ; Na+/Ca2+ exchangers ; Adiponectin anti-sense transgenic mice ; Macrophages ; Inflammation
• 刊名：Molecular Immunology
• 出版年：February, 2014
• 年：2014
• 卷：57
• 期：2
• 页码：141-150
• 全文大小：1163 K

文摘

Adiponectin can protect against inflammation; one of the mechanisms involves direct, inhibition of macrophages (M桅). We postulated that adiponectin anti-sense transgenic (AsTg) mice raised in our laboratory are prone to inflammation because of systemic low adiponectin levels. The writhing response to acetic acid was utilized as an in vivo inflammatory model, and using Ca²⁺, response to the acid was exploited in vitro to evaluate the function of resident peritoneal M桅. The in vivo response to the acid was increased and the Ca²⁺ response of M桅 was enhanced in AsTg mice, compared with those in wild type (WT) mice. In parallel with these enhanced responses, M桅 from AsTg mice augmented TNF-伪 and IL-6 mRNA expression. We further analyzed the enhancement in activity of M桅 from AsTg mice by acid sensing using specific inhibitors, amiloride for acid-sensing ion channels (ASICs) and KB-R7943 for Na⁺/Ca²⁺ exchangers (NCXs). Our results indicated that in AsTg mice, the Ca²⁺ response to the acid was facilitated in M桅 by a low threshold of ASIC1 and NCX1 molecules and the activity of these channel was possibly regulated by adiponectin.