title: TSG-6 protein is crucial for the development of pulmonary hyaluronan deposition, eosinophilia, and airway hyperresponsiveness in a murine model of asthma.
abstract: Hyaluronan (HA) deposition is often correlated with mucosal inflammatory responses, where HA mediates both protective and pathological responses. By modifying the HA matrix, Tnfip6 (TNF-α-induced protein-6; also known as TSG-6 (TNF-stimulated gene-6)) is thought to potentiate anti-inflammatory and anti-plasmin effects that are inhibitory to leukocyte extravasation. In this study, we examined the role of endogenous TSG-6 in the pathophysiological responses associated with acute allergic pulmonary inflammation. Compared with wild-type littermate controls, TSG-6(-/-) mice exhibited attenuated inflammation marked by a significant decrease in pulmonary HA concentrations measured in the bronchoalveolar lavage and lung tissue. Interestingly, despite the equivalent induction of both humoral and cellular Th2 immunity and the comparable levels of cytokines and chemokines typically associated with eosinophilic pulmonary inflammation, airway eosinophilia was significantly decreased in TSG-6(-/-) mice. Most importantly, contrary to their counterpart wild-type littermates, TSG-6(-/-) mice were resistant to the induction of airway hyperresponsiveness and manifested improved lung mechanics in response to methacholine challenge. Our study demonstrates that endogenous TSG-6 is dispensable for the induction of Th2 immunity but is essential for the robust increase in pulmonary HA deposition, propagation of acute eosinophilic pulmonary inflammation, and development of airway hyperresponsiveness. Thus, TSG-6 is implicated in the experimental murine model of allergic pulmonary inflammation and is likely to contribute to the pathogenesis of asthma.
authors.affiliation: Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio 44195, USA.
authors.forename: Shadi
authors.initials: S
authors.lastname: Swaidani
authors.forename: Georgiana
authors.initials: G
authors.lastname: Cheng
authors.forename: Mark E
authors.initials: ME
authors.lastname: Lauer
authors.forename: Manisha
authors.initials: M
authors.lastname: Sharma
authors.forename: Katalin
authors.initials: K
authors.lastname: Mikecz
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Hascall
authors.forename: Mark A
authors.initials: MA
authors.lastname: Aronica
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000276:immunology; D018893:Bronchoalveolar Lavage; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004802:Eosinophilia / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism*; D007249:Inflammation; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; C513057:Tnfaip6 protein, mouse; D006820:Hyaluronic Acid