Decreased expression of SERCA2 in airway smooth muscle cells leads to increased IL-8 release in asthma

作者：Yu, Zhenxi; Shen, Jian; Jiang, Chunming; Li, Xiaoli; Liu, Zhanli; Huang, Xianmei^*

来源：International Journal of Clinical and Experimental Pathology, 2017, 10(4): 4377-4388.

• Asthma
• airway smooth muscle cells
• sarco/endoplasmic reticulum Ca2+-ATPase
• IL-8

Airway smooth muscle cells (ASMCs) secretory and hyperproliferative phenotype in asthma were modulated by the level of free Ca2+ in the cytosol ([Ca2+](i)). Sarco/endoplasmic reticulum Ca2(+-)ATPase (SERCA), an important controller of calcium homeostasis is deficient in asthmatic ASMCs. This study aimed to determine whether SERCA2 deficiency in ASMCs is associated with its excessive IL-8 production. SERCA2 expression, [Ca2+](i) and IL-8 production in primary ASMCs isolated from rats with ovalbumin induced asthma was determined using qRT-PCR, Western blotting, fura PE-3 and ELISA assay respectively. SERCA2 knockdown were performed using siRNA to detect its influence on IL-8 release, NF-kappa B activation, proliferation and migration of normal ASMCs. The NF-kappa B activation was inhibited using PDTC to evaluate its necessity to IL-8 release. IL-8 was depleted using anti-IL-8 antibody to determine whether IL-8 was responsible for enhanced proliferation and migration of ASMCs transfected with SERCA2 siRNA. SERCA2 expression was reduced in asthmatic ASMCs, leading to decreased SR Ca2+ storage and delayed return to base line of [Ca2+](i) after enhanced by bradykinin. SERCA2 knockdown promoted IL-8 mRNA expression and release in normal ASMCs, which was NF-kappa B dependent. In addition, the proliferation and migration of normal ASMCs were also facilitated by SERCA2 knockdown, and IL-8 depletion significantly attenuated ASMCs migration, whereas showed little influence on proliferation. In conclusion, decreased SERCA2 expression in ASMCs during asthma resulted in excessive IL-8 secretion, which in turn accelerates ASMCs migration.

• 出版日期2017
• 单位南京医科大学