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.

Medienart:

Artikel

Erscheinungsjahr:

2005

Erschienen:

2005

Enthalten in:

Zur Gesamtaufnahme - volume:579

Enthalten in:

FEBS letters - 579(2005), 24 vom: 10. Okt., Seite 5430-6

Sprache:

Englisch

Beteiligte Personen:

Lim, Won Chung [VerfasserIn]
Park, Mikyung [VerfasserIn]
Bahn, Jae-Jun [VerfasserIn]
Inoue, Hiroyasu [VerfasserIn]
Lee, Young Joo [VerfasserIn]

Themen:

451W47IQ8X
7S5I7G3JQL
DNA Primers
Dexamethasone
EC 2.7.1.-
EC 2.7.11.24
EC 2.7.12.2
Journal Article
MAP Kinase Kinase 1
MAP Kinase Kinase 2
MAP2K2 protein, human
NF-kappa B
P38 Mitogen-Activated Protein Kinases
RNA, Messenger
Receptors, Glucocorticoid
Research Support, Non-U.S. Gov't
Sodium Chloride

Anmerkungen:

Date Completed 30.11.2005

Date Revised 19.11.2015

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM15810014X