Expression of intelectin-1 in bronchial epithelial cells of asthma is correlated with T-helper 2 (Type-2) related parameters and its function

被引:19
作者
Watanabe, Taiji [1 ]
Chibana, Kazuyuki [1 ]
Shiobara, Taichi [1 ]
Tei, Rinna [1 ]
Koike, Ryosuke [1 ]
Nakamura, Yusuke [1 ]
Arai, Ryo [1 ]
Horigane, Yukiko [1 ]
Shimizu, Yasuo [1 ]
Takemasa, Akihiro [1 ]
Fukuda, Takeshi [2 ]
Wenzel, Sally E. [3 ]
Ishii, Yoshiki [1 ]
机构
[1] Dokkyo Med Univ, Sch Med, Dept Pulm Med & Clin Immunol, Mibu, Tochigi, Japan
[2] Dokkyo Med Univ, Sch Med, 880 Kitakobayashi Mibumachi, Mibu, Tochigi 3210293, Japan
[3] Univ Pittsburgh, Dept Med, Pulm Allergy & Crit Care Med, 3459 Fifth Ave, Pittsburgh, PA 15213 USA
关键词
Intelectin-1; Bronchial asthma; Bronchial epithelial cells; IL-13; Type-2 related parameters; NITRIC-OXIDE; AIRWAY INFLAMMATION; DOUBLE-BLIND; IL-13; RECEPTOR; PATHWAY; FIBROBLASTS; PERIOSTIN; RESPONSES; EFFICACY;
D O I
10.1186/s13223-017-0207-8
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: Intelectin-1 (ITLN-1) is secreted by intestinal goblet cells and detectable in blood. Its expression is increased in IL-13-overexpressing mouse airways. However, its expression and function in human airways is poorly understood. Methods: Distal and proximal bronchial epithelial cells (BECs) were isolated from bronchoscopic brushings of disease control (D-CON), COPD, inhaled corticosteroid-treated asthma (ST-Asthma) and inhaled corticosteroid-naive asthma (SN-Asthma) patients. ITLN-1 mRNA expression in freshly isolated BECs, primary cultured BECs with or without IL-13 and inhibition effects of mometasone furoate (MF) were investigated by quantitative real-time PCR (qPCR). Correlations between ITLN-1 mRNA and Type-2 related parameters (e.g. FeNO, IgE, iNOS, CCL26, periostin and DPP4 mRNA) were analyzed. ITLN-1 protein distribution in asthmatic airway tissue was assessed by immunohistochemistry. Bronchial alveolar lavage (BAL) and serum ITLN-1 protein were measured by ELISA. The effect of recombinant human (rh) ITLN-1 on stimulated production of CXCL10 and phospho(p)-STAT1 expression examined in lung fibroblasts. Results: ITLN-1 mRNA was expressed in freshly isolated BECs and was correlated with Type-2 related parameters. ITLN-1 protein was increased in goblet cells in SN-Asthmatics and increased in SN-Asthmatic BAL fluid. There were no any differences in serum ITLN-1 concentration between ST and SN-Asthma. IL-13 enhanced ITLN-1 expression and inhibited by MF from BECs in vitro, while rhITLN-1 inhibited CXCL10 production and p-STAT1 expression in HFL-1 cells. Conclusion: ITLN-1 is induced by IL-13 and expressed mainly in goblet cells in untreated asthma where its levels correlate with known Type-2 related parameters. Further, ITLN-1 inhibits Type-1 chemokine expression.
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页数:11
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