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-α produces morphological changes in Langerhans cells indistinguishable from those induced by UVB exposure and antibodies against TNF-α have been demonstrated to inhibit UVB-induced immunosuppression in vivo. Objectives: To clarify further the role of TNF-α 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-α. Mice were either irradiated with UVB or injected intradermally with cis-UCA, sensitized with 2,4-dinitrofluoro-benzene, challenged on the ears and the response was measured. Results: The TNFR1R2-/- mice showed hyporesponsiveness in the CHS response compared with wild-type (P lt; 0.001), confirming the proinflammatory role of TNF-α. 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-α signalling is only partially involved in UVB-induced immunosuppression and does not play a major part in the cis-UCA immunosuppression mechanism.
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 / Amerio, ; a and Toto, P.; B, P.; Feliciani, C.; b and Suzuki, C.; a and Shivji, H.; a and Wang, G.; a and Sauder, B.; A, D. N.. - In: BRITISH JOURNAL OF DERMATOLOGY. - ISSN 0007-0963. - 144:5(2001), pp. 952-957. [10.1046/j.1365-2133.2001.04181.x]
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