Tumor necrosis factor-alpha induces renal cyclooxygenase-2 expression in response to hypercalcemia.
The effect of tumor necrosis factor-alpha (TNF) on cyclooxygenase-2 (COX-2) expression in the renal outer medulla (OM) was determined in a model of dihydrotachysterol (DHT)-induced hypercalcemia. Increases in serum calcium and water intake were observed during ingestion of a DHT-containing diet in both wild type (WT) and TNF deficient mice (TNF(-/-)). Polyuria and a decrease in body weight were observed in response to DHT treatment in WT and TNF(-/-) mice. A transient elevation in urinary TNF was observed in WT mice treated with DHT. Moreover, increased urinary levels of prostaglandin E(2) (PGE(2)) and a corresponding increase in COX-2 expression in the OM were observed in WT mice fed DHT. Increased COX-2 expression was not observed in TNF(-/-) mice fed DHT, and the characteristics of PGE(2) synthesis were distinct from those in WT mice. This study demonstrates that COX-2 expression in the OM, secondary to hypercalemia, is TNF-dependent.
Department of Pharmacology, New York Medical College, Valhalla, NY 10595, United States.
Sailaja
S
Battula
Shoujin
S
Hao
Paulina L
PL
Pedraza
Charles T
CT
Stier
Nicholas R
NR
Ferreri
D000818:Animals; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D004097:Dihydrotachysterol; D006934:Hypercalcemia / Q000139:chemically induced / Q000378:metabolism*; D007679:Kidney Medulla / Q000378:metabolism*; D008297:Male; D051379:Mice; D011141:Polyuria / Q000139:chemically induced; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000494:pharmacology* / Q000652:urine
D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D004097:Dihydrotachysterol