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DIFFERENTIAL REGULATION OF â-DEFENSIN EXPRESSION IN HUMAN SKIN BY MICROBIAL STIMULI.

Sørensen2, O.E., Thapa, D.R., Rosenthal, A., Liu, L., Roberts, A.A., Ganz, T. Host Defense Laboratory, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 2Department of Clinical Sciences, Biomedical Center B14, Lund University, Lund, Sweden.
Abstract

This study by researchers at UCLA’s David Geffen School of Medicine and Lund University (Sweden) demonstrated that MatTek’s EpiDerm in vitro human skin tissue equivalent can be used to study the pathways that connect infection and inflammation with the induction of antimicrobial peptides in epithelia. In response to infection, epithelia mount an innate immune response that includes the production of antimicrobial peptides. However, the pathways that connect infection and inflammation with the induction of antimicrobial peptides in epithelia are not understood. Researchers analyzed the molecular links between infection and the expression of three antimicrobial peptides of the â-defensin family, human â-defensin (hBD)-1, hBD-2, and hBD-3 in the human epidermis. After exposure to microbe-derived molecules, both monocytes and lymphocytes stimulated the epidermal expression of hBD-1, hBD-2, and hBD-3. The induced expression of hBD-3 was mediated by transactivation of the epidermal growth factor receptor. The mechanisms of induction of hBD-1 and hBD-3 were distinct from each other and from the IL-1-dependent induction of hBD-2 expression. Thus during inflammation, epidermal expression of â-defensins is mediated by at least three different mechanisms.

Keywords

Anti-microbial, Anti-microbial peptides, Antimicrobial, Antimicrobial peptides, Atopic dermatitis, Beta-defensins, EGF, EpiDerm, EpiDerm-200-3S, Epidermal growth factor receptor, Epidermal keratinocytes, Epithelia, Epithelial Cells, HBD-1, HBD-2, HBD-3, Human beta-defensin 1, Human beta-defensin 2, Human beta-defensin 3, Human skin, IL-1, IL-6, Inflammation, Lymphocytes, Northern blotting, Psoriasis, RNA, TGF-a, TGF-a ELISA, hBD-1, hBD-2, hBD-3

Materials Tested

Amphiregulin, Aprotinin, EGFR Ab, Galardin, HB-EGF ab, Heparin-binding EGF , IL-1ra, IL-6 Ab, INF-a Ab, INF-b Ab, LPS , Mononuclear blood leukocytes (MLBs), Peptidoglycan (PGN), S. Pyogenes, SpeB, TGF-a Ab

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