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アシノ シゲル
芦野 滋 所属 医学部 医学科 職種 非常勤講師 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Less airway inflammation and goblet cell metaplasia in an IL-33-induced asthma model of leptin-deficient obese mice. |
| 掲載誌名 | 正式名：Respiratory research 略 称：Respir Res ISSNコード：1465993X/14659921 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 22(1),pp.166-177 |
| 著者・共著者 | Kurokawa Atsushi†, Kondo Mitsuko, Arimura Ken, Ashino Shigeru, Tagaya Etsuko |
| 発行年月 | 2021/06 |
| 概要 | BACKGROUND:Obesity-associated asthma is a phenotype of severe asthma. Late-onset, non-eosinophilic and female-dominant phenotype is highly symptomatic and difficult to treat. Leptin, an adipokine, exerts an immunomodulatory effect. IL-33 associated with innate immunity induces type 2 inflammation and is present in adipose tissue. The purpose of this study was to elucidate the pathogenesis of obesity-associated asthma by focusing on the interaction between leptin and IL-33.METHODS:In leptin-deficient obese (ob/ob) and wild-type mice, IL-33 was instilled intranasally on three consecutive days. In part of the mice, leptin was injected intraperitoneally prior to IL-33 treatment. The mice were challenged with methacholine, and airway hyperresponsiveness (AHR) was assessed by resistance (Rrs) and elastance (Ers) of the respiratory system using the forced oscillation technique. Cell differentiation, IL-5, IL-13, eotaxin, keratinocyte-derived chemokine (KC) in bronchoalveolar lavage fluid (BALF) and histology of the lung were analyzed. For the in vitro study, NCI-H292 cells were stimulated with IL-33 in the presence or absence of leptin. Mucin-5AC (MUC5AC) levels were measured using an enzyme-linked immunosorbent assay.RESULTS:Ob/ob mice showed greater Rrs and Ers than wild-type mice. IL-33 with leptin, but not IL-33 alone, enhanced Ers rather than Rrs challenged with methacholine in ob/ob mice, whereas it enhanced Rrs alone in wild-type mice. IL-33-induced eosinophil numbers, cytokine levels in BALF, eosinophilic infiltration around the bronchi, and goblet cell metaplasia were less in ob/ob mice than in wild-type mice. However, leptin pretreatment attenuated these changes in ob/ob mice. MUC5AC levels were increased by co-stimulation with IL-33 and leptin in vitro.CONCLUSIONS:Ob/ob mice show innate AHR. IL-33 with leptin, but not IL-33 alone, induces airway inflammation and goblet cell metaplasia and enhances AHR involving peripheral airway closure. This is presumably accel |
| DOI | 10.1186/s12931-021-01763-3 |
| PMID | 34074279 |