title: Mechanism of HBD-3 deficiency in atopic dermatitis.
abstract: Extrinsic atopic dermatitis (EAD) and intrinsic atopic dermatitis (IAD) patients suffer from recurrent bacterial and viral infections. In this study, we demonstrate significantly decreased expression of human beta defensin (HBD)-3, a potent antimicrobial peptide (AMP), in lesional skin of both IAD (p<0.01) and EAD patients (p<0.01), as compared to psoriasis patients. Using primary keratinocytes from EAD and IAD patients, we determined that the deficiency in HBD-3 expression is an acquired rather than a constitutive defect. Furthermore, we demonstrate the down-regulatory effect of IL-4, IL-10, and IL-13 - which are over-expressed in the skin of AD patients - on HBD-3 expression in keratinocytes. Additionally, treatment of EAD skin explants with antibodies against IL-4, IL-10, and IL-13 augmented the expression of HBD-3. These studies suggest that neutralizing the Th2 cytokine milieu in AD skin may augment the innate immune response against bacterial and viral pathogens.
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, The National Jewish Medical and Research Center, Room K926, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Howell
authors.forename: Mark
authors.initials: M
authors.lastname: Boguniewicz
authors.forename: Saveria
authors.initials: S
authors.lastname: Pastore
authors.forename: Natalija
authors.initials: N
authors.lastname: Novak
authors.forename: Thomas
authors.initials: T
authors.lastname: Bieber
authors.forename: Giampiero
authors.initials: G
authors.lastname: Girolomoni
authors.forename: Donald Y M
authors.initials: DY
authors.lastname: Leung
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D011565:Psoriasis / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D023083:beta-Defensins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; C422950:DEFB103A protein, human; D018836:Inflammation Mediators; D023083:beta-Defensins