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Increased cyclooxygenase-2 expression and prostaglandin E2 production in pressurized renal medullary interstitial cells.

Authors :
Carlsen, Inge
Donohue, Kaitlin E.
Jensen, Anja M.
Seizer, Angela L.
Jie Chen
Poppas, Dix P.
Feisen, Diane
Frøkier, Jørgen
Nørregaard, Rikke
Source :
American Journal of Physiology: Regulatory, Integrative & Comparative Physiology. Sep2010, Vol. 299, pR823-R831. 9p. 5 Graphs.
Publication Year :
2010

Abstract

Renat medullary interstitial cells (RMICs) are subjected to osmotic, inflammatory, and mechanical stress as a result of ureteral obstruction, which may influence the expression and activity of cyclooxygenase type 2 (COX-2). Inflammatory stress strongly induces COX-2 in RMICs. To explore the direct effect of mechanical stress on the expression and activity of COX-2, cultured RMICs were subjected to varying amounts of pressure over time using a novel pressure apparatus. COX-2 mRNA and protein were induced following 60 mmHg pressure for 4 and 6 h, respectively. COX-1 mRNA and protein levels were unchanged. PGE2 production in the RMICs was increased when cells were subjected to 60 mmHg pressure for 6 h and was prevented by a selective COX-2 inhibitor. Pharmacological inhibition indicating that pressure-induced COX-2 expression is dependent on p38 MAPK and biochemical knockdown experiments showed that NF-κB might be involved in the COX-2 induction by pressure. Importantly, terminal deoxyneucleotidyl transferase-mediated dUTP nick-end labeling and methylthiazoletetetrazolium assay studies showed that subjecting RMICs to 60 mmHg pressure for 6 h does not affect cell viability, apoptosis, and proliferation. To further examine the regulation of COX-2 in vivo, rats were subjected to unilateral ureteral obstruction (UUO) for 6 and 12 h. COX-2 mRNA and protein level was increased in inner medulla in response to 6- and 12-h UUO. COX-l mRNA and protein levels were unchanged. These findings suggest that in vitro application of pressure recapitulates the effects on RMICs found after in vivo UUO. This directly implicates pressure as an important regulator of renal COX-2 expression. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
03636119
Volume :
299
Database :
Academic Search Index
Journal :
American Journal of Physiology: Regulatory, Integrative & Comparative Physiology
Publication Type :
Academic Journal
Accession number :
53494728
Full Text :
https://doi.org/10.1152/ajpregu.00544.2009