Details

Autor(en) / Beteiligte

• Meyer, Norbert, MD
• Zimmermann, Maya, PhD
• Bürgler, Simone, MSc
• Bassin, Claudio, Dipl Ing FH
• Woehrl, Stefan, MD
• Moritz, Katharina, MD
• Rhyner, Claudio, PhD
• Indermitte, Philippe, Dipl Ing FH
• Schmid-Grendelmeier, Peter, MD
• Akdis, Mübeccel, MD, PhD
• Menz, Günter, MD
• Akdis, Cezmi A., MD

Titel

IL-32 is expressed by human primary keratinocytes and modulates keratinocyte apoptosis in atopic dermatitis

Ist Teil von

• Journal of allergy and clinical immunology, 2010-04, Vol.125 (4), p.858-865.e10

Ort / Verlag

New York, NY: Mosby, Inc

Erscheinungsjahr

2010

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Background Keratinocyte (KC) apoptosis is an important mechanism of eczema and spongiosis in patients with atopic dermatitis (AD) and is mediated by IFN-γ, which is secreted by TH 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-γ, TNF-α, and TH 1 cells in contrast to TH 2, regulatory T (Treg), or TH 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.