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type:Original, Background:Increased severity of asthma is contributed by airway tissue remodeling, which may be associated with chronic allergic inflammation. A recent study revealed the potential capacity of repeated bronchoconstriction, e.g. induced by a muscarine agonist, methacholine(Mch)challenge, to involve in airway remodeling, even though allergic inflammation is not implicated. We have evaluated the influence of repeated bronchoconstriction induced by Mch inhalation on airway remodeling in a murine model of asthma and have examined its machanisms. Methods:Mice were immunized with ovalbumin(OVA), and consequently, challenged by either daily OVA inhalation(the OVA group;a model of asthma with allergic inflammation)or daily Mch inhalation(the Mch group;a model of asthma without allergic inflammation). Lung tissues were obtained and were evaluated histologically after 5, 10, and 15 consecutive inhalation challenges of both OVA and Mch.Results:Eosinophilia in the airway observed only on the OVA group. Subepithelial collagen-band thickness increased also in the OVA group(p<0.01)after 15 challenges, but not in the Mch group. Significant increase in thickness of airway smooth muscle layer and the number of goblet cells were revealed in both the OVA and Mch group after 10(p<0.05 and p<0.01, p<0.01 and p<0.05, respectively, for the comparison of the two challenge groups with the control group)and 15 challenges(p<0.05 and p<0.01, both p< 0.01, respectively, for the comparison with control), further, all these measurements were greater in the OVA group than in the Mch group after both 10 and 15 challenges(both p<0.05 and p<0.01, respectively). An increase in mast cell counts within the airway wall was shown in the OVA group after 10 challenges (p<0.01 compared with control), not in the Mch group at all. Epithelia expression of transforming growthfactor b (TGF-b)increased in both challenge groups after 15 challenges(both p<0.05 compared with control), and was higher than in Mch(p<0.05, identifier:2, identifier:KJ00009786639