Interleukin-33 modulates the expression of human β-defensin 2 in human primary keratinocytes and may influence the susceptibility to bacterial superinfection in acute atopic dermatitis

• Published in: British journal of dermatology (1951) Vol. 167; no. 6; pp. 1386 - 1389
• Main Authors: Alase, A., Seltmann, J., Werfel, T., Wittmann, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-12-2012; Wiley-Blackwell; Oxford University Press
• Subjects: Allergic diseases; Asthma; Atopic dermatitis; Bacteria; beta-Defensins - metabolism; Biological and medical sciences; Cells, Cultured; Cytokines; Data processing; Defensins; Dermatitis; Dermatitis, Atopic - blood; Dermatitis, Atopic - pathology; Dermatology; Eczema; Enzyme-Linked Immunosorbent Assay; Epidermis; Helper cells; Humans; Immunopathology; Interleukin 1; Interleukin 4; Interleukin-1 - metabolism; Interleukin-33; Interleukin-4 - pharmacology; Interleukins - pharmacology; Keratinocytes; Keratinocytes - drug effects; Keratinocytes - metabolism; Lymphocytes T; Medical sciences; Serum - physiology; Skin allergic diseases. Stinging insect allergies; Superinfection; Superinfection - metabolism; Tumor necrosis factor; Tumor necrosis factor- alpha; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - pharmacology; Tumors; Human; Allergy; Immunopathology; Skin disease; Dermatology; Acute; Interleukin; Atopy; Infection; Atopic dermatitis; Bacteriosis; Keratinocyte; Superinfection; Defensin
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/j.1365-2133.2012.11140.x

Summary
Background  Interleukin (IL)‐33 is a member of the IL‐1 family and has been implicated in Th2‐driven allergic diseases such as atopic dermatitis (AD) and asthma. The principal Th2 cytokine IL‐4, found highly expressed in acute allergic eczema, is known to downregulate human β‐defensin 2 (hBD2) expression in human keratinocytes and this is associated with superinfection in patients with AD.
Objectives  To investigate the effect of IL‐33 on the expression of hBD2 in human keratinocytes.
Methods  hBD2 production by stimulated keratinocytes was measured by enzyme‐linked immunosorbent assay.
Results  Our results showed that serum is a very potent inducer of hBD2 and 2·5% human serum was much more potent in inducing hBD2 than 20 ng mL−1 of tumour necrosis factor‐α. Interestingly, serum from patients with AD showed an impaired ability to induce hBD2 in normal keratinocytes. IL‐33 significantly downregulated serum‐induced hBD2. The downregulatory capacity of IL‐33 was found to be 1·5‐ to 2‐fold weaker compared with IL‐4.
Conclusions  Our data suggest that IL‐33 can significantly contribute to the decreased expression of hBD2 in acute eczematous reaction clinically characterized by spongiosis and oozing – thus indicative for contact of the epidermis with serum components.