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

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 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
Volume50
Issue number1
DOIs
Publication statusPublished - Jul 2011

Fingerprint

Cyclooxygenase 2
Histamine
Transcriptional Activation
Lung Neoplasms
1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
Histamine Receptors
Inositol
Calcium Channels
Genetic Promoter Regions
Binding Sites
Inflammation
Gene Expression
Proteins

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Histamine regulates cyclooxygenase 2 gene activation through Orai1-mediated NFκB activation in lung cancer cells. / Huang, Wan Chen; Chai, Chee Yin; Chen, Wei Chiao; Hou, Ming Feng; Wang, Yu Shiuan; Chiu, Yi Ching; Lu, Shiang Ru; Chang, Wen Chang; Juo, Suh Hang Hank; Wang, Jaw Yuan; Chang, Wei Chiao.

In: Cell Calcium, Vol. 50, No. 1, 07.2011, p. 27-35.

Research output: Contribution to journalArticle

Huang, Wan Chen ; Chai, Chee Yin ; Chen, Wei Chiao ; Hou, Ming Feng ; Wang, Yu Shiuan ; Chiu, Yi Ching ; Lu, Shiang Ru ; Chang, Wen Chang ; Juo, Suh Hang Hank ; Wang, Jaw Yuan ; Chang, Wei Chiao. / Histamine regulates cyclooxygenase 2 gene activation through Orai1-mediated NFκB activation in lung cancer cells. In: Cell Calcium. 2011 ; Vol. 50, No. 1. pp. 27-35.
@article{dbb8bf8b9ea14358943c7444d5ddd9bc,
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 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.",
keywords = "COX-2, CRACM1, Histamine, NFkB, Orai1, STIM1, Store-operated calcium channel",
author = "Huang, {Wan Chen} and Chai, {Chee Yin} and Chen, {Wei Chiao} and Hou, {Ming Feng} and Wang, {Yu Shiuan} and Chiu, {Yi Ching} and Lu, {Shiang Ru} and Chang, {Wen Chang} and Juo, {Suh Hang Hank} and Wang, {Jaw Yuan} and Chang, {Wei Chiao}",
year = "2011",
month = "7",
doi = "10.1016/j.ceca.2011.04.004",
language = "English",
volume = "50",
pages = "27--35",
journal = "Cell Calcium",
issn = "0143-4160",
publisher = "Churchill Livingstone",
number = "1",

}

TY - JOUR

T1 - Histamine regulates cyclooxygenase 2 gene activation through Orai1-mediated NFκB activation in lung cancer cells

AU - Huang, Wan Chen

AU - Chai, Chee Yin

AU - Chen, Wei Chiao

AU - Hou, Ming Feng

AU - Wang, Yu Shiuan

AU - Chiu, Yi Ching

AU - Lu, Shiang Ru

AU - Chang, Wen Chang

AU - Juo, Suh Hang Hank

AU - Wang, Jaw Yuan

AU - Chang, Wei Chiao

PY - 2011/7

Y1 - 2011/7

N2 - 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.

AB - 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.

KW - COX-2

KW - CRACM1

KW - Histamine

KW - NFkB

KW - Orai1

KW - STIM1

KW - Store-operated calcium channel

UR - http://www.scopus.com/inward/record.url?scp=79960211428&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960211428&partnerID=8YFLogxK

U2 - 10.1016/j.ceca.2011.04.004

DO - 10.1016/j.ceca.2011.04.004

M3 - Article

C2 - 21605904

AN - SCOPUS:79960211428

VL - 50

SP - 27

EP - 35

JO - Cell Calcium

JF - Cell Calcium

SN - 0143-4160

IS - 1

ER -