Increased expression and a potential anti-inflammatory role of TRAIL in atopic dermatitis.
The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis of many transformed but also of non-transformed cells. In addition, TRAIL receptor activation has been reported to activate non-apoptotic signaling pathways. Here, we report an increased expression of TRAIL in peripheral blood T cells and monocytes from patients with atopic dermatitis (AD) compared with control individuals. High TRAIL expression was also observed in skin-infiltrating T cells of AD patients. Topical tacrolimus treatment reduced the total number of T cells in the skin, but the relative proportion of TRAIL-positive cells within both CD4+ and CD8+ cell populations did not change. TRAIL was demonstrated to induce the expression of interleukin-1 receptor antagonist (IL-1Ra) in keratinocytes in a caspase-independent manner in vitro. Moreover, increased expression of IL-1Ra was observed in keratinocytes of AD lesional skin. These data suggest that TRAIL-expressing inflammatory skin cells may contribute to the epidermal activation of the IL-1Ra gene in AD.
Vassina
Ekatherina
E
Department of Pharmacology, University of Bern, Bern, Switzerland.
Leverkus
Martin
M
Yousefi
Shida
S
Braathen
Lasse R
LR
Simon
Hans-Uwe
HU
Simon
Dagmar
D
D000293:Adolescent; D000328:Adult; D051017:Apoptosis Regulatory Proteins; D003876:Dermatitis, Atopic / Q000276:immunology*; D004817:Epidermis / Q000737:chemistry; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D053590:Interleukin 1 Receptor Antagonist Protein; D015603:Keratinocytes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology*; D008875:Middle Aged; D012795:Sialoglycoproteins / Q000032:analysis / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D008562:Membrane Glycoproteins; D012795:Sialoglycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha