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ATPγS stimulates COX‐2 expression via p38 and p42/p44 MAPK in A549 cells
Author(s) -
Wu WanLing,
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.1120.4
Subject(s) - a549 cell , mapk/erk pathway , p38 mitogen activated protein kinases , small interfering rna , microbiology and biotechnology , transfection , western blot , phosphorylation , cell culture , downregulation and upregulation , chemistry , biology , cell , biochemistry , gene , genetics
In respiratory system, pulmonary alveolar epithelial cells play an important role in the first‐line defense of exteriors and contribute to inflammation. ATP is released from epithelial cells under physiological and pathological conditions. ATP has been shown to induce the expression of COX‐2 in airway epithelial cells and contributes to inflammatory responses. However, the mechanisms underlying ATP‐induced COX‐2 expression and PGE 2 synthesis in human pulmonary A549 cells were not completely understood. In this study, we demonstrated that ATPγS induced COX‐2 protein and mRNA expression in a time‐ and concentration‐dependent manner, which was attenuated by pharmacological inhibitors of MEK1/2 (PD98059), p38 MAPK (SB202190), and NF‐κB (Bay11‐7082), revealed by RT‐PCR and Western blot analyses. Transfection with siRNAs of MEK1, p42, and p38 also inhibited ATPγS‐induced COX‐2 expression. In addition, ATPγS stimulated phosphorylation of p42/p44 MAPK and p38 in a time‐dependent manner, which was attenuated by pretreatment with PD98059 and SB202190. ATPγS‐induced NF‐κB translocation and IκBα degradation was attenuated by PD98059 and SB202190. These results demonstrated that ATPγS‐induced COX‐2 expression via activation of p42/p44 MAPK, p38 and NF‐κB in A549 cells.