Tumor necrosis factor alpha polymorphism correlates with deleterious effects of ultraviolet B light on cutaneous immunity. 1993

V Vincek, and I Kurimoto, and J P Medema, and E Prieto, and J W Streilein
Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33136.

Intradermally injected tumor necrosis factor alpha (TNF-alpha) mimics the effects of UV B light (UVB) radiation and neutralizing anti-TNF-alpha antibodies abolish the deleterious effects of UVB on induction of contact hypersensitivity suggesting that TNF-alpha 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 alpha locus. We have analyzed by the sequence analysis and restriction fragment length polymorphism the Tnf alpha alleles of numerous inbred strains expressing UVB susceptibility (UVB-S) and UVB-resistance (UVB-R). The Tnf alpha 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 alpha 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 alpha 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 alpha compared to UVB-S mice and that the quantitative difference in Tnf alpha produced intracutaneously in response to UVB radiation accounts for the phenotypic traits of UVB-R and UVB-S.

UI MeSH Term Description Entries
D007271 Injections, Intradermal The forcing into the skin of liquid medication, nutrient, or other fluid through a hollow needle, piercing the top skin layer. Intradermal Injections,Injection, Intradermal,Intradermal Injection
D007438 Introns Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes. Intervening Sequences,Sequences, Intervening,Intervening Sequence,Intron,Sequence, Intervening
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D012150 Polymorphism, Restriction Fragment Length Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment. RFLP,Restriction Fragment Length Polymorphism,RFLPs,Restriction Fragment Length Polymorphisms
D002874 Chromosome Mapping Any method used for determining the location of and relative distances between genes on a chromosome. Gene Mapping,Linkage Mapping,Genome Mapping,Chromosome Mappings,Gene Mappings,Genome Mappings,Linkage Mappings,Mapping, Chromosome,Mapping, Gene,Mapping, Genome,Mapping, Linkage,Mappings, Chromosome,Mappings, Gene,Mappings, Genome,Mappings, Linkage
D003877 Dermatitis, Contact A type of acute or chronic skin reaction in which sensitivity is manifested by reactivity to materials or substances coming in contact with the skin. It may involve allergic or non-allergic mechanisms. Contact Dermatitis,Dermatitis Venenata,Eczema, Contact,Hypersensitivity, Contact,Sensitivity, Contact,Contact Dermatitides,Contact Eczema,Contact Hypersensitivities,Contact Hypersensitivity,Contact Sensitivities,Contact Sensitivity,Dermatitides, Contact,Hypersensitivities, Contact,Sensitivities, Contact
D004139 Dinitrofluorobenzene Irritants and reagents for labeling terminal amino acid groups. DNFB,Fluorodinitrobenzene,1-Fluoro-2,4-dinitrobenzene,1 Fluoro 2,4 dinitrobenzene

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