IL-32 is expressed by human primary keratinocytes and modulates keratinocyte apoptosis in atopic dermatitis.
J Allergy Clin Immunol
; 125(4): 858-865.e10, 2010 Apr.
Article
in En
| MEDLINE
| ID: mdl-20227751
ABSTRACT
BACKGROUND:
Keratinocyte (KC) apoptosis is an important mechanism of eczema and spongiosis in patients with atopic dermatitis (AD) and is mediated by IFN-gamma, which is secreted by T(H)1 cells. IL-32 is a proinflammatory cytokine that is involved in the inflammatory processes of rheumatoid arthritis, chronic obstructive pulmonary disease, and Crohn disease. Recently, it was shown that upregulation of IL-32 induces apoptosis.OBJECTIVE:
The aim of the study was to investigate the expression and function of IL-32 in patients with AD.METHODS:
The expression of IL-32 in KCs was analyzed by means of RT-PCR, ELISA, and flow cytometry. Transfections of small interfering RNA were performed in primary KCs, and apoptosis was analyzed by means of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, annexin-V, and 7-amino actinomycin D stainings. Immunofluorescence stainings were used to detect IL-32 in skin biopsy specimens, and serum levels of IL-32 were analyzed by means of ELISA.RESULTS:
We report that IL-32 is expressed in human primary KCs on stimulation with IFN-gamma, TNF-alpha, and T(H)1 cells in contrast to T(H)2, regulatory T (Treg), or T(H)17 cells, which showed no effect. Transfection of primary KCs and artificial skin equivalents with small interfering RNA to IL-32, which resulted in a clear decrease in IL-32 expression, significantly reduced KC apoptosis. Immunofluorescence staining demonstrated that IL-32 was expressed in AD lesional skin, whereas it was present in neither skin biopsy specimens from healthy donors nor in lesional skin from patients with psoriasis. Serum levels of IL-32 from patients with AD correlated with disease severity, but increased serum levels of IL-32 were also detected in asthmatic patients.CONCLUSION:
The present study demonstrates KCs as a source of IL-32, which modulates KC apoptosis and contributes to the pathophysiology of AD.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Keratinocytes
/
Interleukins
/
Apoptosis
/
Dermatitis, Atopic
Limits:
Humans
Language:
En
Journal:
J Allergy Clin Immunol
Year:
2010
Document type:
Article
Affiliation country:
Switzerland