Immune Netw.  2008 Jun;8(2):39-45. 10.4110/in.2008.8.2.39.

Sepsis Mortality in CIITA Deficient Mice is Associated with Excessive Release of High-mobility Group Box 1

• Kim JY
• Kim JH
• Seo JN
• Oh KI

• KMID: 1484312
• DOI: http://doi.org/10.4110/in.2008.8.2.39

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.

Keyword

sepsis; shock; MHC class II transactivator protein; HMGB1 Protein; inflammation; cytokines

MeSH Terms

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
Cytokines
HMGB1 Protein
Nuclear Proteins
Trans-Activators