title: Fungal allergen β-glucans trigger p38 mitogen-activated protein kinase-mediated IL-6 translation in lung epithelial cells.
abstract: In addition to immune cells, airway epithelial cells can contribute to and shape the immune response in the lung by secreting specific cytokines. IL-6 is a key factor in determining the effector fate of CD4(+) T cells. Here we show that under basal conditions, the IL-6 gene is already highly expressed in lung epithelial cells, but not in immune cells resident in the lung. However, upon exposure of the lungs to fungal allergens, the direct contact of β-glucans present in the fungus cell wall with lung epithelial cells is sufficient to trigger the rapid synthesis and secretion of IL-6 protein. This posttranscriptional regulation of IL-6 in response to fungal extracts is mediated by the p38 mitogen-activated protein kinase pathway. The inhalation of β-glucans with a nonallergenic antigen is sufficient to provide an adjuvant effect that leads to mucous hyperplasia in the airways. Thus, β-glucans may constitute a common determinant of the fungal and plant-derived allergens responsible for some of the pathological features in allergic asthma.
authors.affiliation: Division of Immunobiology, Department of Medicine, Vermont Lung Center, University of Vermont College of Medicine, Burlington, USA.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Neveu
authors.forename: Edgar
authors.initials: E
authors.lastname: Bernardo
authors.forename: Jenna L
authors.initials: JL
authors.lastname: Allard
authors.forename: Viswas
authors.initials: V
authors.lastname: Nagaleekar
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Wargo
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Davis
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Whittaker
authors.forename: Mercedes
authors.initials: M
authors.lastname: Rincon
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D000818:Animals; D001232:Aspergillus fumigatus / Q000737:chemistry / Q000276:immunology*; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D047071:beta-Glucans / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology* / Q000378:metabolism
chemical_list: D000485:Allergens; D015850:Interleukin-6; D047071:beta-Glucans; D048051:p38 Mitogen-Activated Protein Kinases