The Role of Cyclooxygenase-2 in Inflammation.
Prostaglandins (PGs) can be synthetized via two isoforms of cyclooxygenase (COX). COX-1 is constitutively expressed in normal tissues, and its activity represent the normal physiological output of PGs. In inflammatory states, the newly discovered COX-2 is rapidly induced, and its activity accounts for the large amounts of PGs seen in inflammation. The commercially available nonsteroidal anti-inflammatory drugs (NSAIDs) are nonselective inhibitors of both COX isoforms; therefore, they provide anti-inflammatory activity as well as side effects associated with COX-1 inhibition. Selective inhibition of COX-2 expression explains at least in part the potent anti-inflammatory activity of steroids. Anti-inflammatory activity of newly developed COX-2 inhibitors, such as NS-398 or SC-58125, suggest a new approach of inflammatory diseases with more efficacious NSAIDs essentially devoid of side effects such as stomach ulcers.
Masferrer
Jaime L.
JL
Department of Inflammatory Diseases Research G.D. Searle T3G, St. Louis, USA, and Analytical Sciences Center, Monsanto Corporate Research.
Zweifel
Ben S.
BS
Colburn
Susan M.
SM
Ornberg
Richard L.
RL
Salvemini
Daniela
D
Isakson
Peter
P
Seibert
Karen
K