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

Wan Chen Huang, Chee Yin Chai, Wei Chiao Chen, Ming Feng Hou, Yu Shiuan Wang, Yi Ching Chiu, Shiang Ru Lu, Wen Chang Chang, Suh Hang Hank Juo, Jaw Yuan Wang, Wei Chiao Chang

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32 Citations (Scopus)


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 10μM 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 -80bp and -250bp, 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.

Original languageEnglish
Pages (from-to)27-35
Number of pages9
JournalCell Calcium
Issue number1
Publication statusPublished - Jul 2011



  • COX-2
  • CRACM1
  • Histamine
  • NFkB
  • Orai1
  • STIM1
  • Store-operated calcium channel

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Huang, W. C., Chai, C. Y., Chen, W. C., Hou, M. F., Wang, Y. S., Chiu, Y. C., Lu, S. R., Chang, W. C., Juo, S. H. H., Wang, J. Y., & Chang, W. C. (2011). Histamine regulates cyclooxygenase 2 gene activation through Orai1-mediated NFκB activation in lung cancer cells. Cell Calcium, 50(1), 27-35. https://doi.org/10.1016/j.ceca.2011.04.004