Role for tumour necrosis factor-alpha receptors in ultraviolet-induced skin tumours.
The biological effects of tumour necrosis factor (TNF)-alpha are mediated through either the TNFR1 or the TNFR2 receptor. In the present study, the effects of ultraviolet (UV) irradiation on skin pathology and tumour promotion were studied in hairless mice deficient in either the TNFR1 or the TNFR2 receptor. SKH-1 hairless mice were crossed with either TNFR1 knockout (KO) mice or TNFR2 KO mice to develop a strain of hairless mice deficient in either of these receptors. Elastosis and other pathological indications of UVB irradiation were not affected by the loss of either receptor. The absence of either receptor, however, resulted in a highly significant reduction in skin tumours in response to UVB irradiation. Inflammatory cell influx following chronic UV irradiation was virtually eliminated in the TNFR1 KO mice, while the TNFR2 KO mice responded to UV irradiation with the normal increase in inflammatory cells throughout the lower and upper dermis. Contact hypersensitivity responses were eliminated in the TNFR2 KO mice, whereas the TNFR1 KO mice retained normal contact hypersensitivity reactions. These studies suggest that TNF-alpha plays no part in the accumulation of excessive elastin in the skin during chronic UVB exposure. However, there appears to be an important role for TNF-alpha in mediating tumorigenesis, distinct from its role in initiating cutaneous immune responses.
Starcher
B
B
University of Texas Health Center at Tyler, Department of Biochemistry, 11937 US Highway 271, Tyler, TX 75708-3154, USA. starcher@uthct.edu
D000818:Animals; D002471:Cell Transformation, Neoplastic; D003877:Dermatitis, Contact / Q000473:pathology / Q000503:physiopathology; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D018345:Mice, Knockout; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000503:physiopathology; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000503:physiopathology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D012867:Skin / Q000473:pathology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology* / Q000503:physiopathology; D014466:Ultraviolet Rays / Q000009:adverse effects*
D018124:Receptors, Tumor Necrosis Factor