Cyclooxygenase 2: Its regulation, role and impact in airway inflammation

Rumzhum, NN; Ammit, AJ

Cyclooxygenase 2: Its regulation, role and impact in airway inflammation

Rumzhum, NN Ammit, AJ

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Publication Type:: Journal Article
Citation:: Clinical and Experimental Allergy, 2016, 46 (3), pp. 397 - 410
Issue Date:: 2016-03-01

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Field	Value	Language
dc.contributor.author	Rumzhum, NN	en_US
dc.contributor.author	Ammit, AJ https://orcid.org/0000-0003-0555-2544	en_US
dc.date.issued	2016-03-01	en_US
dc.identifier.citation	Clinical and Experimental Allergy, 2016, 46 (3), pp. 397 - 410	en_US
dc.identifier.issn	0954-7894	en_US
dc.identifier.uri	http://hdl.handle.net/10453/123692
dc.description.abstract	© 2016 John Wiley & Sons Ltd. 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.	en_US
dc.relation.ispartof	Clinical and Experimental Allergy	en_US
dc.relation.isbasedon	10.1111/cea.12697	en_US
dc.subject.classification	Allergy	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Respiratory Tract Diseases	en_US
dc.subject.mesh	Inflammation	en_US
dc.subject.mesh	Anti-Inflammatory Agents	en_US
dc.subject.mesh	Inflammation Mediators	en_US
dc.subject.mesh	Cytokines	en_US
dc.subject.mesh	Signal Transduction	en_US
dc.subject.mesh	Gene Expression Regulation	en_US
dc.subject.mesh	Cyclooxygenase 2	en_US
dc.subject.mesh	Cyclooxygenase 2 Inhibitors	en_US
dc.title	Cyclooxygenase 2: Its regulation, role and impact in airway inflammation	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	46	en_US
utslib.for	1107 Immunology	en_US
utslib.for	1117 Public Health and Health Services	en_US
utslib.for	1111 Nutrition and Dietetics	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	46	en_US

Abstract:

© 2016 John Wiley & Sons Ltd. 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.

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http://hdl.handle.net/10453/123692