title: Interleukin-1 expression during hyperoxic lung injury in the mouse.
abstract: An important component of the pathophysiologic response to hyperoxia (O2) is pulmonary inflammation, although the roles of specific inflammatory mediators during pulmonary O2 toxicity are not completely known. Interleukin-1 (IL-1) is an early inflammatory mediator and is sufficient to elicit many of the responses associated with acute injury. The IL-1 family comprises two bioactive proteins, IL-1alpha and IL-1beta, and their natural antagonist IL-1ra. Here we report studies of IL-1 regulation during hyperoxic lung injury in the adult mouse. When assayed by Northern blot, increases in IL-1beta mRNA were seen after 2 days of hyperoxia. In contrast, IL-1alpha mRNA was barely detectable before 4 days of hyperoxia. To further understand the cellular origin of IL-1beta expression in lungs, in situ hybridization and immunohistochemical analyses were performed. IL-1beta mRNA or protein was not detected in the lungs of unexposed animals. At 3 days, we observed the accumulation of IL-1beta transcripts in pulmonary interstitial macrophages and in a subset of neutrophils, and immunodetectable IL-1beta protein was co-localized in adjacent sections. At 4 days of exposure, IL-1beta transcripts were widespread in lung tissue, but many areas rich in IL-1beta mRNA were devoid of immunodetectable IL-1beta. However, it is not known whether increased synthesis of IL-1beta or the uncoupling of IL-1beta protein and mRNA accumulation has a role in pathophysiology of pulmonary O2 toxicity.
authors.affiliation: Unité de Recherche de Pédiatrie, Centre de Recherche du CHUL, Centre Hospitalier Universitaire de Québec, Ste-Foy, Canada. Bruno.Piedboeuf@crchul.ulaval.ca
authors.forename: B
authors.initials: B
authors.lastname: Piedboeuf
authors.forename: S
authors.initials: S
authors.lastname: Horowitz
authors.forename: C J
authors.initials: CJ
authors.lastname: Johnston
authors.forename: M
authors.initials: M
authors.lastname: Gamache
authors.forename: S
authors.initials: S
authors.lastname: Bélanger
authors.forename: P E
authors.initials: PE
authors.lastname: Poubelle
authors.forename: S E
authors.initials: SE
authors.lastname: Welty
authors.forename: R H
authors.initials: RH
authors.lastname: Watkins
mesh_terms: D000818:Animals; D018496:Hyperoxia / Q000378:metabolism*; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010100:Oxygen / Q000633:toxicity; D010477:Perfusion; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger; D010100:Oxygen