Abstracts / Prostaglandins
L other Lipid Mediators 59 (1999) 1-235
REGULATION OF CYCLOOXYGENASE- 1 AND -2 IN KNOCKOUT CELLS AND MICE Leslie R. Ballou Department of Veterans Affairs Medical Center and the University of Tennessee Center for the Health Sciences, Memphis, TN 38104. Email: [email protected]
Prostaglandin E (PGE ) production in lung cells derived from wild-type, cyclooxygenase-1 (COX-l-‘-) or cyiloox$genase-2 (COX-2’-) deficient mice was examined after treatment with proinflammatory cytokines. Compared with their wild-type (COX-l+‘+/COX-2+‘+)counterparts, COX- 14 or COX-24 cells exhibited substantially enhanced expression of the remaining functional COX gene. Both basal and cytokine-induced expression of cytosolic phospholipase A (cPLA > was also more pronounced in both COX-1 and COX-2 deficient cells. Thus the pot&tial for’cells to alter and thereby compensate for defects in the expression of specific genes such as COX has significant clinical implications given the centra1 role of COX in pathophysiology and the widespread use of COX inhibitors as therapeutic agents. Zn vivo, analysis of mRNA levels in tissues obtained from COX knockout mice by RT-PCR indicate that ‘compensatory’ COX isoenzyme expression occurs in a tissue-specific manner and furthermore, that inflammatory responses in vivo are altered as a result of differential COX isoenzyme expression. Recent data on the effects of COX isoenzyme deficiency using in vivo models of inflammation, fever and disease wil1 be presented.