Rethinking the role of tumour necrosis factor-α in ultraviolet (UV) B-induced immunosuppression:: altered immune response in UV-irradiated TNFR1R2 gene-targeted mutant mice

被引:19
作者
Amerio, P
Toto, P
Feliciani, C
Suzuki, H
Shivji, G
Wang, B
Sauder, DN
机构
[1] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada
[2] Univ G DAnnunzio, Chieti, Italy
关键词
cis-urocanic acid; contact hypersensitivity; cytokines; immunosuppression; tumour necrosis factor-alpha; ultraviolet radiation;
D O I
10.1046/j.1365-2133.2001.04181.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Background Ultraviolet (UV) B-induced immunosuppression, implicated in the pathogenesis of skin cancers, is postulated to be mediated in part by cis-urocanic acid (cis-UCA) via tumour necrosis factor (TNF)-alpha. TNF-alpha produces morphological changes in Langerhans cells indistinguishable from those induced by UVB exposure and antibodies against TNF-alpha have been demonstrated to inhibit UVB-induced immunosuppression in vivo. Objectives To clarify further the role of TNF-alpha in UVB-induced immunosuppression and in cis-UCA immunosuppression. Methods We performed a contact hypersensitivity (CHS) assay on gene-targeted mutant mice (TNFR1R2-/-) lacking genes for both receptors (p55 and p75) for TNF-alpha. Mice were either irradiated with UVB or injected intradermally with cis-UCA, sensitized with 2,4-dinitrofluorobenzene, challenged on the ears and the response was measured. Results The TNFR1R2-/- mice showed hyporesponsiveness in the CHS response compared with wild-type (P < 0.001), confirming the proinflammatory role of TNF-alpha. However, significant suppression of CHS was seen after irradiation and after cis-UCA injection in both locally (sensitization on irradiated site; P < 0.05) and systemically (sensitization on non-irradiated site; P < 0.05) sensitized wild-type and gene-targeted mice. Conclusions These results demonstrate that TNF-alpha signalling is only partially involved in UVB-induced immunosuppression and does not play a major part in the cis-UCA immunosuppression mechanism.
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页码:952 / 957
页数:6
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