Sepsis Mortality in CIITA Deficient Mice is Associated with Excessive Release of High-mobility Group Box 1.
- Author:
Ji Young KIM
1
;
Ju Hyun KIM
;
Jae Nam SEO
;
Kwon Ik OH
Author Information
- Publication Type:Original Article
- Keywords: sepsis; shock; MHC class II transactivator protein; HMGB1 Protein; inflammation; cytokines
- MeSH: Animals; Cytokines; Down-Regulation; HMGB1 Protein; Immunosuppression; Inflammation; Ligation; Lymphocytes; Major Histocompatibility Complex; Mice; Nuclear Proteins; Punctures; Recombination, Genetic; Sepsis; Shock; Survival Rate; Trans-Activators
- From:Immune Network 2008;8(2):39-45
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND: Down regulation of major histocompatibility complex class II transactivator (CIITA) has been identified as a major factor of immunosuppression in sepsis and the level of CIITA expression inversely correlates with the degree of severity. However, it has not been fully elucidated whether the lower expression of CIITA is a cause of disease process or a just associated sign. Here we determined whether the CIITA deficiency decreased survival rate using murine sepsis model. METHODS: Major histocompatibility complex class II (MHC-II) deficient, CIITA deficient and wild type B6 mice were subjected to cecal ligation puncture (CLP) surgery. CIITA and recombination activation gene (RAG)-1 double deficient mice were generated to test the role of lymphocytes in CIITA-associated sepsis progression. RESULTS: Sepsis mortality was enhanced in CIITA deficient mice, not by impaired bacterial clearance resulted from CD4 T cell depletion, but hyper-inflammatory response such as excessive release of a pro-inflammatory cytokine, high-mobility group box 1 (HMGB1). CONCLUSION: Our results demonstrate that CIITA deficiency affects the course of sepsis via the unexpected function of CIITA, regulation of cytokine release.
