title: Characterization of lung inflammation and its impact on macrophage function in aging.
abstract: Systemic inflammation that occurs with increasing age (inflammaging) is thought to contribute to the increased susceptibility of the elderly to several disease states. The elderly are at significant risk for developing pulmonary disorders and infectious diseases, but the contribution of inflammation in the pulmonary environment has received little attention. In this study, we demonstrate that the lungs of old mice have elevated levels of proinflammatory cytokines and a resident population of highly activated pulmonary macrophages that are refractory to further activation by IFN-γ. The impact of this inflammatory state on macrophage function was determined in vitro in response to infection with M.tb. Macrophages from the lungs of old mice secreted more proinflammatory cytokines in response to M.tb infection than similar cells from young mice and also demonstrated enhanced M.tb uptake and P-L fusion. Supplementation of mouse chow with the NSAID ibuprofen led to a reversal of lung and macrophage inflammatory signatures. These data indicate that the pulmonary environment becomes inflammatory with increasing age and that this inflammatory environment can be reversed with ibuprofen.
authors.affiliation: Department of Microbial Infection and Immunity, College of Medicine, and Center for Microbial Interface Biology, The Ohio State University, Columbus Ohio, USA.
authors.forename: Cynthia H
authors.initials: CH
authors.lastname: Canan
authors.affiliation: Department of Microbial Infection and Immunity, College of Medicine, and Center for Microbial Interface Biology, The Ohio State University, Columbus Ohio, USA.
authors.forename: Nandan S
authors.initials: NS
authors.lastname: Gokhale
authors.affiliation: Department of Microbial Infection and Immunity, College of Medicine, and Center for Microbial Interface Biology, The Ohio State University, Columbus Ohio, USA.
authors.forename: Bridget
authors.initials: B
authors.lastname: Carruthers
authors.affiliation: Department of Microbial Infection and Immunity, College of Medicine, and Center for Microbial Interface Biology, The Ohio State University, Columbus Ohio, USA.
authors.forename: William P
authors.initials: WP
authors.lastname: Lafuse
authors.affiliation: Department of Microbial Infection and Immunity, College of Medicine, and Center for Microbial Interface Biology, The Ohio State University, Columbus Ohio, USA.
authors.forename: Larry S
authors.initials: LS
authors.lastname: Schlesinger
authors.affiliation: Department of Microbial Infection and Immunity, College of Medicine, and Center for Microbial Interface Biology, The Ohio State University, Columbus Ohio, USA.
authors.forename: Jordi B
authors.initials: JB
authors.lastname: Torrelles
authors.affiliation: Department of Microbial Infection and Immunity, College of Medicine, and Center for Microbial Interface Biology, The Ohio State University, Columbus Ohio, USA joanne.turner@osumc.edu.
authors.forename: Joanne
authors.initials: J
authors.lastname: Turner
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D007052:Ibuprofen / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000494:pharmacology; D008168:Lung / Q000254:growth & development / Q000276:immunology / Q000473:pathology*; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008561:Membrane Fusion; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology; D010588:Phagosomes / Q000502:physiology; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D011994:Recombinant Proteins; D007371:Interferon-gamma; D007052:Ibuprofen
keywords: M. tuberculosis; age; inflammaging