title: Prostaglandin E2 induction during mouse adenovirus type 1 respiratory infection regulates inflammatory mediator generation but does not affect viral pathogenesis.
abstract: Respiratory viruses cause substantial disease and are a significant healthcare burden. Virus-induced inflammation can be detrimental to the host, causing symptoms during acute infection and leading to damage that contributes to long-term residual lung disease. Prostaglandin E2 (PGE2) is a lipid mediator that is increased in response to many viral infections, and inhibition of PGE2 production during respiratory viral infection often leads to a decreased inflammatory response. We tested the hypothesis that PGE2 promotes inflammatory responses to mouse adenovirus type 1 (MAV-1) respiratory infection. Acute MAV-1 infection increased COX-2 expression and PGE2 production in wild type mice. Deficiency of the E prostanoid 2 receptor had no apparent effect on MAV-1 pathogenesis. Virus-induced induction of PGE2, IFN-γ, CXCL1, and CCL5 was reduced in mice deficient in microsomal PGE synthase-1 (mPGES-1(-/-) mice). However, there were no differences between mPGES-1(+/+) and mPGES-1(-/-) mice in viral replication, recruitment of leukocytes to airways or lung inflammation. Infection of both mPGES‑1(+/+) and mPGES-1(-/-) mice led to protection against reinfection. Thus, while PGE2 promotes the expression of a variety of cytokines in response to acute MAV-1 infection, PGE2 synthesis does not appear to be essential for generating pulmonary immunity.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Mary K
authors.initials: MK
authors.lastname: McCarthy
authors.forename: Rachael E
authors.initials: RE
authors.lastname: Levine
authors.forename: Megan C
authors.initials: MC
authors.lastname: Procario
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McDonnell
authors.forename: Lingqiao
authors.initials: L
authors.lastname: Zhu
authors.forename: Peter
authors.initials: P
authors.lastname: Mancuso
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Crofford
authors.forename: David M
authors.initials: DM
authors.lastname: Aronoff
authors.forename: Jason B
authors.initials: JB
authors.lastname: Weinberg
mesh_terms: D000256:Adenoviridae / Q000276:immunology / Q000472:pathogenicity*; D000818:Animals; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D060888:Real-Time Polymerase Chain Reaction; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
chemical_list: D018946:Chemokine CCL5; D054360:Chemokine CXCL1; D007371:Interferon-gamma; D015232:Dinoprostone