title: Cyclooxygenase 2: its regulation, role and impact in airway inflammation.
abstract: Cyclooxygenase 2 (COX-2: official gene symbol - PTGS2) has long been regarded as playing a pivotal role in the pathogenesis of airway inflammation in respiratory diseases including asthma. COX-2 can be rapidly and robustly expressed in response to a diverse range of pro-inflammatory cytokines and mediators. Thus, increased levels of COX-2 protein and prostanoid metabolites serve as key contributors to pathobiology in respiratory diseases typified by dysregulated inflammation. But COX-2 products may not be all bad: prostanoids can exert anti-inflammatory/bronchoprotective functions in airways in addition to their pro-inflammatory actions. Herein, we outline COX-2 regulation and review the diverse stimuli known to induce COX-2 in the context of airway inflammation. We discuss some of the positive and negative effects that COX-2/prostanoids can exert in in vitro and in vivo models of airway inflammation, and suggest that inhibiting COX-2 expression to repress airway inflammation may be too blunt an approach; because although it might reduce the unwanted effects of COX-2 activation, it may also negate the positive effects. Evidence suggests that prostanoids produced via COX-2 upregulation show diverse actions (and herein we focus on prostaglandin E2 as a key example); these can be either beneficial or deleterious and their impact on respiratory disease can be dictated by local concentration and specific interaction with individual receptors. We propose that understanding the regulation of COX-2 expression and associated receptor-mediated functional outcomes may reveal number of critical steps amenable to pharmacological intervention. These may prove invaluable in our quest towards future development of novel anti-inflammatory pharmacotherapeutic strategies for the treatment of airway diseases.
authors.affiliation: Faculty of Pharmacy, University of Sydney, Sydney, NSW, Australia.
authors.forename: N N
authors.initials: NN
authors.lastname: Rumzhum
authors.affiliation: Faculty of Pharmacy, University of Sydney, Sydney, NSW, Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: Ammit
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D012140:Respiratory Tract Diseases / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D018836:Inflammation Mediators; D051546:Cyclooxygenase 2