title: Interleukin (IL)-4, IL-13, and IL-17A differentially affect the profibrotic and proinflammatory functions of fibrocytes from asthmatic patients.
abstract: Fibrocytes contribute to the fibrotic changes most frequently observed in forms of asthma where inflammation is driven by T helper type 2 (Th2) cells. The mechanisms that regulate the profibrotic function of asthmatic fibrocytes are largely unknown. We isolated circulating fibrocytes from patients with allergen-exacerbated asthma, who showed the presence of fibrocytes, together with elevated concentrations of interleukin (IL)-4 and IL-13 and slightly increased concentrations of the Th17 cell-derived IL-17A, in induced sputum. Fibrocytes stimulated with IL-4 and IL-13 produced high levels of collagenous and non-collagenous matrix components and low levels of proinflammatory cytokines. Conversely, fibrocytes stimulated with IL-17A proliferated and released proinflammatory factors that may promote neutrophil recruitment and airway hyperresponsiveness. IL-17A also indirectly increased α-smooth muscle actin but not collagen expression in fibrocytes. Thus, fibrocytes may proliferate and express a predominant profibrotic or proinflammatory phenotype in asthmatic airways depending on the local concentrations of Th2- and Th17-derived cytokines.
authors.affiliation: Avail Biomedical Research Institute, Basel, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Bellini
authors.forename: M A
authors.initials: MA
authors.lastname: Marini
authors.forename: L
authors.initials: L
authors.lastname: Bianchetti
authors.forename: M
authors.initials: M
authors.lastname: Barczyk
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.forename: S
authors.initials: S
authors.lastname: Mattoli
mesh_terms: D000328:Adult; D056151:Airway Remodeling / Q000187:drug effects; D001249:Asthma / Q000150:complications / Q000276:immunology* / Q000628:therapy; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D018793:Interleukin-13 / Q000032:analysis / Q000494:pharmacology; D020381:Interleukin-17 / Q000032:analysis / Q000494:pharmacology; D015847:Interleukin-4 / Q000032:analysis / Q000494:pharmacology; D008297:Male; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D013183:Sputum / Q000737:chemistry; D055815:Young Adult
chemical_list: D018836:Inflammation Mediators; D018793:Interleukin-13; D020381:Interleukin-17; D015847:Interleukin-4; D003094:Collagen