Differential regulation of beta-defensin expression in human skin by microbial stimuli.
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. We analyzed the molecular links between infection and the expression of three antimicrobial peptides of the beta-defensin family, human beta-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 beta-defensins is mediated by at least three different mechanisms.
Sørensen
Ole E
OE
Host Defense Laboratory, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. Ole_E.Sorensen@medkem.lu.se
Thapa
Dharma R
DR
Rosenthal
Adam
A
Liu
Lide
L
Roberts
Alice A
AA
Ganz
Tomas
T
D001427:Bacterial Toxins / Q000633:toxicity; D001483:Base Sequence; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008214:Lymphocytes / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D023083:beta-Defensins / Q000235:genetics*
D001427:Bacterial Toxins; C406407:DEFB1 protein, human; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D018076:DNA, Complementary; D012333:RNA, Messenger; D023083:beta-Defensins