Histamine regulates cyclooxygenase 2 gene activation through Orai1-mediated NFκB activation in lung cancer cells

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• 作者：Wan-Chen Huang^b ; ¹ ; Chee-Yin Chai^e ; ¹ ; Wei-Chiao Chen^a ; Ming-Feng Hou^c ; ^d ; Yu-Shiuan Wang^a ; Yi-Ching Chiu^a ; Shiang-Ru Lu^g ; Wen-Chang Chang^b ; ^f ; Suh-Hang Hank Juo^a ; ^c ; Jaw-Yuan Wang^a ; ^c ; ^d ; ^h ; Wei-Chiao Chang^a ; ^c ; ^{wcc@kmu.edu.tw"" rel=""nofollow}
• 关键词：STIM1 ; Orai1 ; Histamine ; COX-2 ; NFkB ; CRACM1 ; Store-operated calcium channel
• 刊名：Cell Calcium
• 出版年：2011
• 出版时间：July 2011
• 年：2011
• 卷：50
• 期：1
• 页码：27-35
• 全文大小：1441 K

文摘

Histamine, an important chemical mediator, has been shown to regulate inflammation and allergic responses. Stimulation of histamine receptors results in a significant increase in cytoplasmic Ca²⁺, which could be mediated by inositol trisphosphate (IP₃)-dependent store-operated Ca²⁺ channels (SOC). However, the link between histamine-mediated signaling and activation of inflammatory genes such as cyclooxygenase 2 (COX-2) is still unknown. Our study indicated that the COX-2 protein was highly expressed in human lung cancer cells. Following stimulation with 10 μM of histamine, both store-operated Ca²⁺ entry (SOCE) and COX-2 gene expression were evoked. Histamine-mediated COX-2 activation can be prevented by 2-APB and SKF-96365, SOC channel inhibitors. In addition, deletion analysis of the COX-2 promoter suggested that the region between −80 bp and −250 bp, which contains NFκB binding sites, is the key element for histamine-mediated signaling. Knocking down ORAI1, one of the essential molecules of store-operated calcium channels, attenuated histamine-mediated COX-2 expression and NFκB activation. These results indicated that ORAI1-mediated NFκB activation was an important signaling pathway, responsible for transmitting histamine signals that trigger inflammatory reactions.