Stromal interaction molecule 1 (STIM1) and Orai1 mediate histamine-evoked calcium entry and nuclear factor of activated T-cells (NFAT) signaling in human umbilical vein endothelial cells. Academic Article uri icon


  • Histamine is an important immunomodulator involved in allergic reactions and inflammatory responses. In endothelial cells, histamine induces Ca(2+) mobilization by releasing Ca(2+) from the endoplasmic reticulum and eliciting Ca(2+) entry across the plasma membrane. Herein, we show that histamine-evoked Ca(2+) entry in human umbilical vein endothelial cells (HUVECs) is sensitive to blockers of Ca(2+) release-activated Ca(2+) (CRAC) channels. RNA interference against STIM1 or Orai1, the activating subunit and the pore-forming subunit of CRAC channels, respectively, abolishes this histamine-evoked Ca(2+) entry. Furthermore, overexpression of dominant-negative CRAC channel subunits inhibits while co-expression of both STIM1 and Orai1 enhances histamine-induced Ca(2+) influx. Interestingly, gene silencing of STIM1 or Orai1 also interrupts the activation of calcineurin/nuclear factor of activated T-cells (NFAT) pathway and the production of interleukin 8 triggered by histamine in HUVECs. Collectively, these results suggest a central role of STIM1 and Orai1 in mediating Ca(2+) mobilization linked to inflammatory signaling of endothelial cells upon histamine stimulation.

published proceedings

  • J Biol Chem

altmetric score

  • 2.85

author list (cited authors)

  • Zhou, M., Zheng, H., Si, H., Jin, Y., Peng, J. M., He, L., ... Zhang, S. L.

citation count

  • 27

complete list of authors

  • Zhou, Meng-Hua||Zheng, Hongying||Si, Hongjiang||Jin, Yixin||Peng, Jasmine M||He, Lian||Zhou, Yubin||Muñoz-Garay, Carlos||Zawieja, David C||Kuo, Lih||Peng, Xu||Zhang, Shenyuan L

publication date

  • October 2014