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IL-12 prevents the inhibitory effects of cis-urocanic acid on tumor antigen presentation by Langerhans cells: implications for photocarcinogenesis.

Abstract
UV radiation induces skin cancer primarily by its DNA-damaging properties, but also by its capacity to suppress the immune system. The photoisomer of urocanic acid (UCA), cis-UCA, is an important mediator of UV-induced immunosuppression and is involved in the inhibition of tumor immunity. The immunomodulatory cytokine IL-12 is known to counteract many of the immunosuppressive effects of UV radiation, including UV-induced immune tolerance. In this study, we addressed whether IL-12 also reverts the immunosuppressive activities of cis-UCA. Cis-UCA inhibits the ability of Langerhans cells to present tumor Ags for primary and secondary tumor immune responses. IL-12 treatment completely prevented the suppression by cis-UCA. IL-12 also protected mice from cis-UCA-induced suppression of contact hypersensitivity responses. To study the effects of cis-UCA on Ag-processing and Ag-presenting function in vitro, Langerhans cells were treated with UCA isomers and incubated with OVA or OVA peptide(323-339) before exposure to OVA-specific transgenic T cells. Cis-, but not trans-UCA suppressed Ag presentation, which was completely reversed upon addition of IL-12. Since these findings suggest that cis-UCA may play an important role in photocarcinogenesis by inhibiting a tumor immune response, mice were chronically UVB irradiated to induce skin cancer. Whereas all mice in the control groups developed tumors, mice treated with a mAb with specificity for cis-UCA showed a significantly reduced tumor incidence. These data strongly indicate the importance of cis-UCA during photocarcinogenesis and support the concept of counteracting cis-UCA as an alternative strategy to prevent UV-induced skin cancer, possibly via the application of IL-12.
AuthorsS Beissert, D Rühlemann, T Mohammad, S Grabbe, A El-Ghorr, M Norval, H Morrison, R D Granstein, T Schwarz
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 167 Issue 11 Pg. 6232-8 (Dec 01 2001) ISSN: 0022-1767 [Print] United States
PMID11714785 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • Immune Sera
  • Immunosuppressive Agents
  • Interleukin-12
  • Urocanic Acid
Topics
  • Animals
  • Antigen Presentation (drug effects, immunology)
  • Antigens, Neoplasm (immunology, metabolism)
  • Dermatitis, Contact (immunology, prevention & control)
  • Epitopes, T-Lymphocyte (immunology)
  • Female
  • Immune Sera (administration & dosage)
  • Immunization, Passive
  • Immunosuppressive Agents (antagonists & inhibitors, pharmacology)
  • Injections, Intraperitoneal
  • Interleukin-12 (physiology)
  • Langerhans Cells (drug effects, immunology, metabolism)
  • Lymphocyte Activation (drug effects)
  • Mice
  • Mice, Inbred A
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Neoplasms, Radiation-Induced (immunology)
  • Skin Neoplasms (immunology, prevention & control)
  • T-Lymphocytes (drug effects, immunology)
  • Tumor Cells, Cultured
  • Ultraviolet Rays
  • Urocanic Acid (administration & dosage, antagonists & inhibitors, immunology, pharmacology)

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