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Cigarette smoke induces cyclooxygenase‐2 expression in human tracheal smooth muscle cells
Author(s) -
Yang YaLing,
Kou YuRu,
Yang ChuenMao
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.897.2
Subject(s) - p38 mitogen activated protein kinases , pyrrolidine dithiocarbamate , mapk/erk pathway , phosphorylation , chemistry , kinase , microbiology and biotechnology , signal transduction , protein kinase a , nf κb , gene silencing , biochemistry , biology , gene
Induction of COX‐2 expression by cigarette smoke (CS) may play an important role in airway inflammation. Here, the roles of mitogen‐activated protein kinases (MAPKs) and nuclear factor‐κB (NF‐κB) pathways for CS‐induced COX‐2 expression were investigated in human smooth muscle cells (HTSMCs). CS‐induced expression of COX‐2 protein and mRNA was inhibited by inhibitors of MEK1/2 (U0126), p38 (SB202190), and NF‐κB (helenalin). The involvement of p42/p44 MAPK and p38 in these responses was further confirmed by that transfection with small interference RNAs (siRNA) of p42, and p38 attenuated CS‐induced COX‐2 expression. Consistently, CS‐stimulated phosphorylation of p42/p44 MAPK and p38 was attenuated by pretreatment with U0126 or SB202190, respectively. In addition, CS‐stimulated translocation of NF‐κB into the nucleus and degradation of IκB‐α was blocked by helenalin, U0126, or SB202190. Moreover, CS‐induced responses were inhibited by pretreatment with antioxidant reagents such as N‐aceytlcysteine, apocynin, diphenyleneiodonium chloride, and pyrrolidine dithiocarbamate, indicating the involvement of ROS generation in CS‐induced COX‐2 expression and MAPKs phosphorylation. Taken together, these results suggest that in HTSMCs, activation of p42/p44 MAPK and p38 pathways converged to NF‐κB translocation is essential for CS‐induced COX‐2 gene expression. These results provide new insight into the mechanisms by which CS may promote inflammatory responses in the airway disease.