Fungal allergen beta-glucans trigger p38 mitogen-activated protein kinase-mediated IL-6 translation in lung epithelial cells
Program in Molecular Medicine
Medical Subject Headings
Allergens; Animals; Aspergillus fumigatus; Asthma; CD4-Positive T-Lymphocytes; Cells, Cultured; Epithelial Cells; Gene Expression Regulation; Interleukin-6; Lung; MAP Kinase Signaling System; Mice; Mice, Knockout; Respiratory Mucosa; beta-Glucans; p38 Mitogen-Activated Protein Kinases
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Immunity | Molecular Biology
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 beta-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 beta-glucans with a nonallergenic antigen is sufficient to provide an adjuvant effect that leads to mucous hyperplasia in the airways. Thus, beta-glucans may constitute a common determinant of the fungal and plant-derived allergens responsible for some of the pathological features in allergic asthma.
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Citation: Am J Respir Cell Mol Biol. 2011 Dec;45(6):1133-41. doi: 10.1165/rcmb.2011-0054OC. Epub 2011 Jun 3. Link to article on publisher's site
Neveu, Wendy A.; Bernardo, Edgar; Allard, Jenna L.; Nagaleekar, Viswas; Wargo, Matthew J.; Davis, Roger J.; Iwakura, Yoichiro; Whittaker, Laurie A.; and Rincon, Mercedes, "Fungal allergen beta-glucans trigger p38 mitogen-activated protein kinase-mediated IL-6 translation in lung epithelial cells" (2011). Davis Lab. 37.