title: Histamine regulates cyclooxygenase 2 gene activation through Orai1-mediated NFκB activation in lung cancer cells.
abstract: 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 Ca(2+), which could be mediated by inositol trisphosphate (IP(3))-dependent store-operated Ca(2+) 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 Ca(2+) 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.
authors: Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan. wcc@kmu.edu.tw
authors: Wan-Chen
authors: WC
authors: Huang
authors: Chee-Yin
authors: CY
authors: Chai
authors: Wei-Chiao
authors: WC
authors: Chen
authors: Ming-Feng
authors: MF
authors: Hou
authors: Yu-Shiuan
authors: YS
authors: Wang
authors: Yi-Ching
authors: YC
authors: Chiu
authors: Shiang-Ru
authors: SR
authors: Lu
authors: Wen-Chang
authors: WC
authors: Chang
authors: Suh-Hang Hank
authors: SH
authors: Juo
authors: Jaw-Yuan
authors: JY
authors: Wang
authors: Wei-Chiao
authors: WC
authors: Chang