HindIII liposomes suppress delayed-type hypersensitivity responses in vivo and induce epidermal IL-10 in vitro.
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.
Nishigori
C
C
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Yarosh
D
D
O'Connor
A
A
Shreedhar
V K
VK
Ullrich
S E
SE
Cox
P
P
Kripke
M L
ML
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002176:Candida albicans / Q000276:immunology; D002460:Cell Line; D002474:Cell-Free System / Q000276:immunology; D004249:DNA Damage / Q000276:immunology; D015247:Deoxyribonuclease HindIII / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D015603:Keratinocytes / Q000166:cytology; D008081:Liposomes / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D014466:Ultraviolet Rays
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D007519:Isoantigens; D008081:Liposomes; D016753:Interleukin-10; D015247:Deoxyribonuclease HindIII