Universität zu Köln

Haarmann, Helge, Steiner, Tamara, Schreiber, Frauke, Heinrich, Annina, Zweigner, Janine, N'Guessan, Philippe Dje and Slevogt, Hortense (2015). The role and regulation of Moraxella catarrhalis-induced human beta-defensin 3 expression in human pulmonary epithelial cells. Biochem. Biophys. Res. Commun., 467 (1). S. 46 - 53. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1090-2104

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Abstract

Background: Bacterial colonisation with Moraxella catarrhalis may partly sustain chronic inflammation in the lower airways of patients with chronic obstructive pulmonary disease (COPD). In addition, this bacterium causes infectious exacerbations of COPD, which often necessitate treatment with antibiotics. Antimicrobial peptides are the body's own antibiotic substances with bactericidal and bacteriostatic, as well as immunomodulatory function. In particular, human beta-defensin 3 (hBD-3) exerts an antimicrobial effect against an extraordinarily broad spectrum of pathogens. We therefore investigated the role of hBD-3 in infections of pulmonary epithelial cells with M. catarrhalis. Methods: The antimicrobial activity of hBD-3 vs. M. catarrhalis was evaluated in an antimicrobial susceptibility assay. We analyzed hBD-3 secretion of M. catarrhalis-infected pulmonary epithelial cells using ELISA. The role of M. catarrhalis-specific virulence factors, toll-like receptors (TLR) 2 and 4, MAPK pathways, and transcription factors AP-1 and NF-kappa B in the induction and regulation of hBD-3 expression were explored with specific inhibitors, small interference RNA, Western Blot, and chromatin immunoprecipitation (ChIP) assays. Results: HBD-3 exhibited a strong bactericidal effect against M. catarrhalis. M. catarrhalis induced hBD-3 expression in pulmonary epithelial cells, which was dependent on M. catarrhalis membranous lipoolygosaccharide (LOS), while the surface proteins UspA1 and UspA2 were not involved. Gene silencing of TLR2, but not TLR4, led to a reduced hBD-3 secretion after stimulation with M. catarrhalis or M. catarrhalis LOS. Inhibition of MAPKs ERK1/2 and JNK, but not p38, reduced hBD-3 secretion. HBD-3 expression was mediated through the recruitment of AP-1 to the hBD-3 gene promoter and was independent of NF-kappa B. Conclusion: The immune response of pulmonary epithelial cells towards M. catarrhalis involves secretion of hBD-3, which has a bactericidal effect against this pathogen. Binding of M. catarrhalis virulence factor LOS to TLR2 causes an ERK1/2- and JNK-dependent induction of AP-1-related transcription of the hBD-3 gene, resulting in the production and secretion of hBD-3. (C) 2015 Published by Elsevier Inc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Haarmann, Helge UNSPECIFIED UNSPECIFIED UNSPECIFIED Steiner, Tamara UNSPECIFIED UNSPECIFIED UNSPECIFIED Schreiber, Frauke UNSPECIFIED UNSPECIFIED UNSPECIFIED Heinrich, Annina UNSPECIFIED UNSPECIFIED UNSPECIFIED Zweigner, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED N'Guessan, Philippe Dje UNSPECIFIED UNSPECIFIED UNSPECIFIED Slevogt, Hortense UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-387189
DOI:	10.1016/j.bbrc.2015.09.126
Journal or Publication Title:	Biochem. Biophys. Res. Commun.
Volume:	467
Number:	1
Page Range:	S. 46 - 53
Date:	2015
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Place of Publication:	SAN DIEGO
ISSN:	1090-2104
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INFLAMMATORY IMMUNE-RESPONSE; GROWTH-FACTOR RECEPTOR; NF-KAPPA-B; HUMAN BETA-DEFENSIN-3; ANTIMICROBIAL PEPTIDES; RESPIRATORY-TRACT; TNF-ALPHA; ACTIVATION; INFECTION; PATHWAYS Multiple languages Biochemistry & Molecular Biology; Biophysics Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38718