Abstract
BackgroundIntelectin-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.MethodsDistal 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-naïve 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.ResultsITLN-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.ConclusionITLN-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.
Highlights
Intelectin-1 (ITLN-1) is secreted by intestinal goblet cells and detectable in blood
IL-13-induced periostin [8] and dipeptidyl peptidase-4 (DPP4) can be measured in peripheral blood and are used as biomarkers to predict the efficacy of anti-IL-13 antibodies in human asthma patients [9,10,11]
fractional exhaled nitric oxide (FeNO) in Steroid Naïve (SN)-Asthma were significantly higher than SN-Asthma (**p < 0.01)
Summary
Intelectin-1 (ITLN-1) is secreted by intestinal goblet cells and detectable in blood. Its expression and function in human airways is poorly understood. Type-2 cytokines (interleukin (IL)-4, IL-5, and IL-13) are known to play a substantial pathobiological role in many cases These cytokines, including IL-13 contribute to a Type2-high molecular asthma phenotype in about 50% of patients with asthma, and are widely believed to play important roles in asthma pathophysiology [1,2,3,4,5,6,7]. IL-13-induced periostin [8] and DPP4 can be measured in peripheral blood and are used as biomarkers to predict the efficacy of anti-IL-13 antibodies in human asthma patients [9,10,11]. Human ITLN-1 is a prophylactic soluble lectin discovered that recognizes
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