TY - JOUR
T1 - Mechanism of HBD-3 deficiency in atopic dermatitis
AU - Howell, Michael D.
AU - Boguniewicz, Mark
AU - Pastore, Saveria
AU - Novak, Natalija
AU - Bieber, Thomas
AU - Girolomoni, Giampiero
AU - Leung, D. Y M
PY - 2006/12
Y1 - 2006/12
N2 - 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.
AB - 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.
KW - Antimicrobial peptides
KW - Cytokines
KW - Extrinsic atopic dermatitis
KW - Intrinsic atopic dermatitis
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U2 - 10.1016/j.clim.2006.08.008
DO - 10.1016/j.clim.2006.08.008
M3 - Article
C2 - 17015038
AN - SCOPUS:33751116548
VL - 121
SP - 332
EP - 338
JO - Clinical Immunology
JF - Clinical Immunology
SN - 1521-6616
IS - 3
ER -