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.
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.


OBJECTIVE
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.
Leeds Institute of Molecular Medicine, Division of Rheumatic and Musculoskeletal Disease, LMBRU, University of Leeds, Leeds, UK. a.a.alase@leeds.ac.uk
A
A
Alase
J
J
Seltmann
T
T
Werfel
M
M
Wittmann
D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000097:blood / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D000067596:Interleukin-33; D015847:Interleukin-4 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D044967:Serum / Q000502:physiology; D015163:Superinfection / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D023083:beta-Defensins / Q000378:metabolism*
C106641:DEFB4A protein, human; C506536:IL33 protein, human; D007375:Interleukin-1; D000067596:Interleukin-33; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; D015847:Interleukin-4