This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vincek, V. Articles by Streilein, J. W. Search for Related Content PubMed PubMed Citation Articles by Vincek, V. Articles by Streilein, J. W.

Tumor Necrosis Factor Polymorphism Correlates with Deleterious Effects of Ultraviolet B Light on Cutaneous Immunity¹

Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33136

Intradermally injected tumor necrosis factor (TNF-) mimics the effects of UV B light (UVB) radiation and neutralizing anti-TNF- antibodies abolish the deleterious effects of UVB on induction of contact hypersensitivity suggesting that TNF- is the major mediator of UVB effects on cutaneous immunity. In the present study we have shown that in lipopolysaccharide-sensitive inbred strains of mice, the ability of acute, low-dose UVB radiation to impair the induction of contact hypersensitivity to dinitrofluorobenzene is genetically determined by polymorphic alleles at the Tnf locus. We have analyzed by the sequence analysis and restriction fragment length polymorphism the Tnf alleles of numerous inbred strains expressing UVB susceptibility (UVB-S) and UVB-resistance (UVB-R). The Tnf alleles of all UVB-R, but not UVB-S, strains contain a BamHI site in the first intron. Moreover, the 5' regulatory region of the Tnf allele of UVB-R mice possesses a (CA)₁₄ minirepeat that is located immediately 5' of the cytokine response element nearest the tumor-associated transplantation antigen box. By contrast, the Tnf alleles of UVB-S mice display repeats of 14 at this site. It is proposed that the unique microsatellite of UVB-R mice impairs transcriptional efficiency at Tnf compared to UVB-S mice and that the quantitative difference in Tnf produced intracutaneously in response to UVB radiation accounts for the phenotypic traits of UVB-R and UVB-S.

¹ This work was supported in part by NIH Grant ROI AI-22072, the American Cancer Society Grant ACS-PDT-383-A, and the American Cancer Society Florida Division Grant F93UM-1.

² To whom requests for reprints should be addressed, at Department of Microbiology and Immunology, University of Miami School of Medicine, P.O. Box 016960 R-138, Miami, FL 33136.

Received 12/ 1/92. Accepted 12/31/92.

This article has been cited by other articles:

				S. L. Walker and A. R. Young An action spectrum (290 320 nm) for TNF{alpha} protein in human skin in vivo suggests that basal-layer epidermal DNA is the chromophore PNAS, November 27, 2007; 104(48): 19051 - 19054. [Abstract] [Full Text] [PDF]

				L. E. MATESIC, E. L. NIEMITZ, A. DE MAIO, and R. H. REEVES Quantitative trait loci modulate neutrophil infiltration in the liver during LPS-induced inflammation FASEB J, November 1, 2000; 14(14): 2247 - 2254. [Abstract] [Full Text]

				P. H. Hart, M. A. Grimbaldeston, G. J. Swift, A. Jaksic, F. P. Noonan, and J. J. Finlay-Jones Dermal Mast Cells Determine Susceptibility to Ultraviolet B-induced Systemic Suppression of Contact Hypersensitivity Responses in Mice J. Exp. Med., June 15, 1998; 187(12): 2045 - 2053. [Abstract] [Full Text] [PDF]

				M. Gorivodsky, I. Zemlyak, H. Orenstein, S. Savion, A. Fein, A. Torchinsky, and V. Toder TNF-{alpha} Messenger RNA and Protein Expression in the Uteroplacental Unit of Mice with Pregnancy Loss J. Immunol., May 1, 1998; 160(9): 4280 - 4288. [Abstract] [Full Text] [PDF]