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.