Hin dIII Liposomes Suppress Delayed-Type Hypersensitivity Responses In Vivo and Induce Epidermal IL-10 In Vitro
Abstract
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.
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UV-induced DNA breaks in Langerhans cells could induce suppressive cytokines such as IL-10 and inhibit contact hypersensitivity responses.
“UV-induced DNA breaks in LCs could induce suppressive cytokines such as IL-10 and inhibit CHS responses [63].”
From Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy (2013) · cites this paper as [63]
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“Third, in the past we have been able to induce cytokine production and systemic immune suppression by inducing nonspecific DNA damage with HindIII-containing liposomes (45).”
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“Consistent with this finding, it has been shown that DNA-damage induced by the treatment of mice with HindIII-containing liposomes causes double-strand breaks and induces immunosuppression (Nishigori et al., 1998).”
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- Authors
- Nishigori, C., Yarosh, D., O’Connor, A., K. Shreedhar, V., Ullrich, S. E., Cox, P., & Kripke, M. L.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- AGI Dermatics , Freeport, NY 11520
- Department of Immunology, University of Texas M. D. Anderson Cancer Center , Houston, TX 77030
- Corresponding author
- Nishigori, Chikako
- Cox, Patricia
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1998-09
- Volume
- 161
- Issue
- 6
- Pages
- 2684-2691
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1669321027
- Cited by
- 22
- References
- 0
- Citations by year
- 2026: 1 · 2013: 1
- FWCI
- 0.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA-16672, R01CA052457, R01CA52457, P30CA016672)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- delayed-type hypersensitivity, immunosuppression, DNA double-strand breaks, UV-B radiation, cyclobutane pyrimidine dimers, keratinocytes, Candida albicans, alloantigen, regulatory T cells, immunomodulatory cytokines, DNA damage
- MeSH terms
- Epidermal Cells, Animals, Antibodies, Monoclonal, Candida albicans, Cell Line, Cell-Free System, DNA Damage, Epidermis, Female, Hypersensitivity, Delayed, Immunosuppressive Agents, Isoantigens, Liposomes, Mice, Inbred BALB C, Mice, Inbred C3H, Ultraviolet Rays, Deoxyribonuclease HindIII, Keratinocytes, Interleukin-10, Mice
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