Thymidine dinucleotides inhibit contact hypersensitivity and activate the gene for tumor necrosis factor α

Ponciano D Cruz, Martin Leverkus, Irene Dougherty, Michelle J. Gleason, Mark Eller, Mina Yaar, Barbara A. Gilchrest

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

DNA is a target for ultraviolet-B-induced inhibition of contact hypersensitivity, and small DNA fragments such as thymidine dinucleotides (pTpT) can simulate several ultraviolet-induced effects. To determine whether pTpT mimics the suppressive influence of ultraviolet-B on contact hypersensitivity, we compared the effects of topical application of pTpT with those of ultraviolet-B irradiation on C57BL/6 mice sensitized to dinitrofluorobenzene. Mice pretreated with pTpT or ultraviolet-B irradiation showed markedly suppressed ear swelling responses to dinitrofluorobenzene challenge. Because tumor necrosis factor α mediates ultraviolet-B-induced suppression of contact hypersensitivity, and because pTpT exerts many ultraviolet-mimetic effects by augmenting mRNA and protein levels of effector molecules, we asked if pTpT mimics ultraviolet-B's upregulatory influence on tumor necrosis factor α expression. Using transgenic mice carrying a chloramphenicol acetyl transferase reporter linked to the tumor necrosis factor α promoter, we examined effects of ultraviolet-B irradiation versus intradermal injection of pTpT on tumor necrosis factor α gene transcription. Both treatments induced cutaneous chloramphenicol acetyl transferase activity. Ultraviolet-B or pTpT treatment of cultured dermal fibroblasts from these mice also stimulated chloramphenicol acetyl transferase activity. To determine whether human cells responded similarly, a well-differentiated ultraviolet-responsive human squamous cell carcinoma line was treated with pTpT. pTpT increased tumor necrosis factor α mRNA expression and protein secretion in a dose-dependent manner. Our findings expand the spectrum of ultraviolet effects mimicked by pTpT to include inhibition of contact hypersensitivity and activation of the tumor necrosis factor α gene. These results support the hypothesis that DNA photoproducts and/or their repair intermediates trigger many of the biologic consequences of ultraviolet irradiation.

Original languageEnglish (US)
Pages (from-to)253-258
Number of pages6
JournalJournal of Investigative Dermatology
Volume114
Issue number2
DOIs
StatePublished - 2000

Fingerprint

Contact Dermatitis
Thymidine
Tumor Necrosis Factor-alpha
Genes
Chloramphenicol
Transferases
Irradiation
Dinitrofluorobenzene
DNA
Intradermal Injections
Messenger RNA
Skin
Transcription
Fibroblasts
Inbred C57BL Mouse
Transgenic Mice
Ear
Swelling
Squamous Cell Carcinoma
Proteins

Keywords

  • Cytokines
  • Delayed type hypersensitivity
  • Human
  • Immunomodulators
  • Rodent

ASJC Scopus subject areas

  • Dermatology

Cite this

Thymidine dinucleotides inhibit contact hypersensitivity and activate the gene for tumor necrosis factor α. / Cruz, Ponciano D; Leverkus, Martin; Dougherty, Irene; Gleason, Michelle J.; Eller, Mark; Yaar, Mina; Gilchrest, Barbara A.

In: Journal of Investigative Dermatology, Vol. 114, No. 2, 2000, p. 253-258.

Research output: Contribution to journalArticle

Cruz, Ponciano D ; Leverkus, Martin ; Dougherty, Irene ; Gleason, Michelle J. ; Eller, Mark ; Yaar, Mina ; Gilchrest, Barbara A. / Thymidine dinucleotides inhibit contact hypersensitivity and activate the gene for tumor necrosis factor α. In: Journal of Investigative Dermatology. 2000 ; Vol. 114, No. 2. pp. 253-258.
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