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BY IL-1 SIGNALING, MONOCYTE-DERIVED CELLS DRAMATICALLY ENHANCE THE EPIDERMAL ANTIMICROBIAL RESPONSE TO LIPOPOLYSACCHARIDE.

Liu1, L., Roberts2, A. A., and Ganz1, T. 1Will Rogers Pulmonary Research Laboratory, Departments of Medicine and Pathology. 2Department of Pathology, Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Abstract

Epithelia react to microbial pathogens by mounting a defensive response that includes the production of antimicrobial peptides. In this study, we show that, in human epidermal cultures, Escherichia coli LPS was a very weak direct inducer of human β-defensin (HBD)-2 mRNA and peptide, but the induction was greatly amplified when monocyte-derived cells (MoDeC) acted as intermediaries between LPS and the epidermis. IL-1R antagonist largely reversed the effect of MoDeC on epidermal HBD-2, indicating that, from among the many products of MoDeC, IL-1 was the dominant inducer of HBD-2 syntheses. In normal fresh human skin, which contains Langerhans cells and other myeloid cell types, in addition to keratinocytes, LPS also induced HBD-2 in an IL-1-dependent manner. In DNA microarray expression studies, HBD-2 was one of the most abundant mRNAs induced in epidermis by LPS-treated MoDeC, and its induction was reversed by IL-1Ra. Thus, epidermal response to LPS is potently amplified by MoDeC through IL-1-mediated signalling, leading to a selective increase in the synthesis of the antimicrobial peptide HBD-2. This pattern of responses establishes a key role for both IL-1 and HBD-2 in the host defense reaction of the epidermis.

Keywords

Anti-microbial, Anti-microbial activity, Anti-microbial peptide, Anti-microbial peptides, Antimicrobial, Antimicrobial activity, Antimicrobial peptide, Antimicrobial peptides, DNA microarray, DNA microarray expression studies, EPI-200-3S, EpiDerm, Eschenichia LPS, Eschenichia coli, Gene expression, HBD-2, Host defense, Human beta-defensin-2 (HBD-2), IL-1, IL-1 signaling, IL-1r, IL-1ra, Lipopolysaccharide, Microarray, Microbial pathogens, Monocyte-derived cells (MoDeC), Pathogens

Materials Tested

Lipopolysaccharide

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