Genipin attenuates sepsis-induced immunosuppression through inhibition of T lymphocyte apoptosis
- Authors
- Kim J.-S.[Kim J.-S.]; Kim S.-J.[Kim S.-J.]; Lee S.-M.[Lee S.-M.]
- Issue Date
- 2015
- Keywords
- Apoptosis; Genipin; Immunosuppression; Regulatory T cell; Sepsis; T helper 1/T helper 2 cytokine shift
- Citation
- International Immunopharmacology, v.27, no.1, pp.15 - 23
- Journal Title
- International Immunopharmacology
- Volume
- 27
- Number
- 1
- Start Page
- 15
- End Page
- 23
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/47915
- DOI
- 10.1016/j.intimp.2015.04.034
- Abstract
- Abstract Sepsis, a systemic inflammatory response to infection, initiates a complex immune response consisting of an early hyperinflammatory response and a subsequent hypoinflammatory response that impairs the removal of infectious organisms. The importance of sepsis-induced immunosuppression and its contribution to mortality has recently emerged. Apoptotic depletion of T lymphocytes is a critical cause of immunosuppression in the late phase of sepsis. Genipin is a major active compound of gardenia fruit that has anti-apoptotic and anti-microbial properties. This study investigated the mechanisms of action of genipin on immunosuppression in the late phase of sepsis. Mice received genipin (1, 2.5 and 5 mg/kg, i.v.) at 0 (immediately) and 24 h after cecal ligation and puncture (CLP). Twenty-six hours after CLP, the spleen and blood were collected. Genipin improved the survival rate compared to controls. CLP increased the levels of FADD, caspase-8 and caspase-3 protein expression, which were attenuated by genipin. Genipin increased the level of anti-apoptotic B-cell lymphoma-2 protein expression, while it decreased the level of pro-apoptotic phosphorylated-Bim protein expression in CLP. CLP decreased the CD4+ and CD8+ T cell population, while it increased the regulatory T cell (Treg) population and the level of cytotoxic T lymphocyte-associated antigen 4 protein expression on Treg. These changes were attenuated by genipin. The splenic levels of interferon-γ and interleukin (IL)-2 were reduced, while the levels of IL-4 and IL-10 increased after CLP. Genipin attenuated these alterations. These findings suggest that genipin reduces immunosuppression by inhibiting T lymphocyte apoptosis in the late phase of sepsis. © 2015 Elsevier B.V. All rights reserved.
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Collections - Pharmacy > Department of Pharmacy > 1. Journal Articles
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