Hypertonic sodium chloride induction of cyclooxygenase-2 occurs independently of NF-kappaB and is inhibited by the glucocorticoid receptor in A549 cells.
Cellular response to a hypertonic environment is important for fluid clearance in the lung. Hypertonicity modulates prostaglandin synthesis by influencing cyclooxygenase-2 (COX-2) expression in tissues such as liver and kidney via a mitogen-activated protein kinase (MAPK)-dependent pathway. However, little is known about COX-2 expression in response to hypertonicity in the lung. COX-2 mRNA accumulation induced by hypertonic NaCl was detected after 1 h of treatment, and COX-2 mRNA continued to accumulate until 18 h, the longest time point examined, in human alveolar epithelial A549 cells. This induction was a transcriptional event that occurred in the absence of the protein synthesis inhibitor cycloheximide and was the result of enhanced promoter activity, as examined with the use of full-length COX-2 promoter-driven reporter plasmids. The induction of COX-2 expression by hypertonic NaCl did not require the activation of NF-kappaB. The p38 MAPK inhibitor, SB203580, or MEK1/2 inhibitor, U0126, inhibited hypertonic induction of COX-2 expression. We examined whether the hypertonic induction of COX-2 was under the influence of glucocorticoid; we found that COX-2 promoter activity and mRNA and protein levels were depressed by dexamethasone and antagonized by the glucocorticoid receptor (GR) antagonist RU486. Our data demonstrate that the induction of COX-2 expression by hypertonic NaCl occurs independently of NF-kappaB and is inhibited by the GR in A549 cells.
Lim
Won Chung
WC
College of Engineering, Institute of Biotechnology, Department of Bioscience and Biotechnology, Sejong University, Kwang-Jin-Gu, Seoul, Republic of Korea.
Park
Mikyung
M
Bahn
Jae-Jun
JJ
Inoue
Hiroyasu
H
Lee
Young Joo
YJ
D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology*; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012965:Sodium Chloride / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D017931:DNA Primers; D016328:NF-kappa B; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D012965:Sodium Chloride; D003907:Dexamethasone; C482128:MAP2K2 protein, human; D048051:p38 Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2