IL-4 and IL-13 exposure during mucociliary differentiation of bronchial epithelial cells increases antimicrobial activity and expression of antimicrobial peptidesReport as inadecuate




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Respiratory Research

, 12:59

First Online: 01 December 2011Received: 22 April 2010Accepted: 02 May 2011

Abstract

The airway epithelium forms a barrier against infection but also produces antimicrobial peptides AMPs and other inflammatory mediators to activate the immune system. It has been shown that in allergic disorders, Th2 cytokines may hamper the antimicrobial activity of the epithelium. However, the presence of Th2 cytokines also affects the composition of the epithelial layer which may alter its function. Therefore, we investigated whether exposure of human primary bronchial epithelial cells PBEC to Th2 cytokines during mucociliary differentiation affects expression of the human cathelicidin antimicrobial protein hCAP18-LL-37 and human beta defensins hBD, and antimicrobial activity.

PBEC were cultured at an air-liquid interface ALI for two weeks in the presence of various concentrations of IL-4 or IL-13. Changes in differentiation and in expression of various AMPs and the antimicrobial proteinase inhibitors secretory leukocyte protease inhibitor SLPI and elafin were investigated as well as antimicrobial activity.

IL-4 and IL-13 increased mRNA expression of hCAP18-LL-37 and hBD-2. Dot blot analysis also showed an increase in hCAP18-LL-37 protein in apical washes of IL-4-treated ALI cultures, whereas Western Blot analysis showed expression of a protein of approximately 4.5 kDa in basal medium of IL-4-treated cultures. Using sandwich ELISA we found that also hBD-2 in apical washes was increased by both IL-4 and IL-13. SLPI and elafin levels were not affected by IL-4 or IL-13 at the mRNA or protein level. Apical wash obtained from IL-4- and IL-13-treated cultures displayed increased antimicrobial activity against Pseudomonas aeruginosa compared to medium-treated cultures. In addition, differentiation in the presence of Th2 cytokines resulted in increased MUC5AC production as has been shown previously.

These data suggest that prolonged exposure to Th2 cytokines during mucociliary differentiation contributes to antimicrobial defence by increasing the expression and release of selected antimicrobial peptides and mucus.

Keywordshuman lung cell differentiation allergy inflammation Electronic supplementary materialThe online version of this article doi:10.1186-1465-9921-12-59 contains supplementary material, which is available to authorized users.

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Author: Suzanne Zuyderduyn - Dennis K Ninaber - Jasmijn A Schrumpf - Marianne AJA van Sterkenburg - Renate M Verhoosel - Frans A

Source: https://link.springer.com/







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