%0 Journal Article
%T Oxidative stress induced Interleukin-32 mRNA expression in human bronchial epithelial cells
%A Megumi Kudo
%A Emiko Ogawa
%A Daisuke Kinose
%A Akane Haruna
%A Tamaki Takahashi
%A Naoya Tanabe
%A Satoshi Marumo
%A Yuma Hoshino
%A Toyohiro Hirai
%A Hiroaki Sakai
%A Shigeo Muro
%A Hiroshi Date
%A Michiaki Mishima
%J Respiratory Research
%D 2012
%I BioMed Central
%R 10.1186/1465-9921-13-19
%X Human bronchial epithelial (HBE) cells were stimulated with H2O2 and IFN¦Ã, and IL-32 expression was evaluated. The cell viability was confirmed by MTT assay. The intracellular signaling pathways regulating IL-32 expression were investigated by examining the regulatory effects of MAPK inhibitors and JAK inhibitor after treatment with H2O2 and IFN¦Ã, and by using a ChIP assay to identify transcription factors (i.e. c-Jun, CREB) binding to the IL-32 promoter. Promoter activity assays were conducted after mutations were introduced into binding sites of c-Jun and CREB in the IL-32 promoter. IL-32 expression was also examined in HBE cells in which the expression of either c-Jun or CREB was knocked out by siRNA of indicated transcription factors.There were no significant differences of cell viability among groups. After stimulation with H2O2 or IFN¦Ã for 48 hours, IL-32 expression in HBE cells was increased by IFN¦Ã and synergistically upregulated by the addition of H2O2. The H2O2 augmented IFN¦Ã induced IL-32 mRNA expression was suppressed by a JNK inhibitor, but not by MEK inhibitor, p38 inhibitor, and JAK inhibitor I. Significant binding of c-Jun and CREB to the IL-32 promoter was observed in the IFN¦Ã + H2O2 stimulated HBE cells. Introducing mutations into the c-Jun/CREB binding sites in the IL-32 promoter prominently suppressed its transcriptional activity. Further, knocking down CREB expression by siRNA resulted in significant suppression of IL-32 induction by IFN¦Ã and H2O2 in HBE cells.IL-32 expression in airway epithelium may be augmented by inflammation and oxidative stress, which may occur in COPD acute exacerbation. c-Jun and CREB are key transcriptional factors in IFN¦Ã and H2O2 induced IL-32 expression.Chronic obstructive pulmonary disease (COPD) is characterized by non-fully reversible airflow obstruction and persistent inflammation in the airways and lung parenchyma [1-3]. Airway epithelial cells are one of the most important sources of inflammatory mediators that
%K COPD
%K acute exacerbation
%K IFN¦Ã
%U http://respiratory-research.com/content/13/1/19