title: Influences of innate immunity, autophagy, and fibroblast activation in the pathogenesis of lung fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by accumulation of extracellular matrix (ECM) and impaired gas exchange. The pathobiological mechanisms that account for disease progression are poorly understood but likely involve alterations in innate inflammatory cells, epithelial cells, and fibroblasts. Thus we seek to review the most recent literature highlighting the complex roles of neutrophils and macrophages as both promoters of fibrosis and defenders against infection. With respect to epithelial cells and fibroblasts, we review the data suggesting that defective autophagy promotes the fibrogenic potential of both cell types and discuss new evidence related to matrix metalloproteinases, growth factors, and cellular metabolism in the form of lactic acid generation that may have consequences for promoting fibrogenesis. We discuss potential cross talk between innate and structural cell types and also highlight literature that may help explain the limitations of current IPF therapies.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan;
authors.forename: David N
authors.initials: DN
authors.lastname: O'Dwyer
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; Graduate Program in Immunology, University of Michigan, Ann Arbor, Michigan; and.
authors.forename: Shanna L
authors.initials: SL
authors.lastname: Ashley
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan bmoore@umich.edu.
authors.forename: Bethany B
authors.identifier: http://orcid.org/0000-0003-3051-745X
authors.initials: BB
authors.lastname: Moore
mesh_terms: D000818:Animals; D001343:Autophagy; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007113:Immunity, Innate; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D019344:Lactic Acid / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000502:physiology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D019344:Lactic Acid; D020782:Matrix Metalloproteinases
keywords: epithelial cells; fibroblasts; fibrosis; innate immunity; lung