HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nishigori, C. Articles by Kripke, M. L. Search for Related Content PubMed PubMed Citation Articles by Nishigori, C. Articles by Kripke, M. L.

HindIII Liposomes Suppress Delayed-Type Hypersensitivity Responses In Vivo and Induce Epidermal IL-10 In Vitro¹

Chikako Nishigori^*, Daniel Yarosh, Adrienne O’Connor, Vijay K. Shreedhar^*, Stephen E. Ullrich^*, Patricia Cox^* and Margaret L. Kripke^2,*

^* Department of Immunology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; and AGI Dermatics, Freeport, NY 11520

Considerable evidence suggests that ultraviolet-B (UV-B) radiation suppresses certain immune responses through the induction of cyclobutane pyrimidine dimers in DNA. To determine whether induction of other forms of DNA damage in the skin mimicked the immunosuppressive effects of UV-B radiation, we produced double-strand breaks in the DNA of epidermal cells with HindIII restriction endonuclease encapsulated in liposomes. Application of these liposomes, but not liposomes containing inactive HindIII or an irrelevant endonuclease, to the skin of C3H mice suppressed the induction of delayed-type hypersensitivity responses to Candida albicans and alloantigen and induced IL-10 production in the epidermis. Treatment of the Pam212 murine keratinocyte cell line with these liposomes in vitro induced immunosuppressive activity and IL-10 in culture supernatants. Unlike UV-B irradiation, however, HindIII in liposomes failed to induce suppressor T cell activity in vivo or in vitro. We conclude that double-strand breaks in DNA of epidermal cells can induce immunosuppression and up-regulate the production of immunomodulatory cytokines; however, either DNA damage alone does not account for all the immunosuppressive properties of UV-B irradiation, or cyclobutane pyrimidine dimers differ qualitatively from double-strand breaks in their biologic consequences. These studies raise the possibility that drugs causing DNA damage may induce cytokine dysregulation and immune suppression in addition to cytotoxicity.

This article has been cited by other articles:

				J. Jans, G. A. Garinis, W. Schul, A. van Oudenaren, M. Moorhouse, M. Smid, Y.-G. Sert, A. van der Velde, Y. Rijksen, F. R. de Gruijl, et al. Differential Role of Basal Keratinocytes in UV-Induced Immunosuppression and Skin Cancer Mol. Cell. Biol., November 15, 2006; 26(22): 8515 - 8526. [Abstract] [Full Text] [PDF]

				N. Y. Crowe, J. M. Coquet, S. P. Berzins, K. Kyparissoudis, R. Keating, D. G. Pellicci, Y. Hayakawa, D. I. Godfrey, and M. J. Smyth Differential antitumor immunity mediated by NKT cell subsets in vivo J. Exp. Med., November 7, 2005; 202(9): 1279 - 1288. [Abstract] [Full Text] [PDF]

				J. P. Walterscheid, S. E. Ullrich, and D. X. Nghiem Platelet-activating Factor, a Molecular Sensor for Cellular Damage, Activates Systemic Immune Suppression J. Exp. Med., January 14, 2002; 195(2): 171 - 179. [Abstract] [Full Text] [PDF]

				H. Miyauchi-Hashimoto, K. Kuwamoto, Y. Urade, K. Tanaka, and T. Horio Carcinogen-Induced Inflammation and Immunosuppression Are Enhanced in Xeroderma Pigmentosum Group A Model Mice Associated with Hyperproduction of Prostaglandin E2 J. Immunol., May 1, 2001; 166(9): 5782 - 5791. [Abstract] [Full Text] [PDF]

				L. L. Hill, V. K. Shreedhar, M. L. Kripke, and L. B. Owen-Schaub A Critical Role for Fas Ligand in the Active Suppression of Systemic Immune Responses by Ultraviolet Radiation J. Exp. Med., April 19, 1999; 189(8): 1285 - 1294. [Abstract] [Full Text] [PDF]