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- Title
Overexpression of HO-1 Contributes to Sepsis-Induced Immunosuppression by Modulating the Th1/Th2 Balance and Regulatory T-Cell Function.
- Authors
Seong-Jin Yoon; So-Jin Kim; Sun-Mee Lee; Yoon, Seong-Jin PhD; Kim, So-Jin PhD; Lee, Sun-Mee PhD; Yoon, Seong-Jin; Kim, So-Jin; Lee, Sun-Mee
- Abstract
<bold>Background: </bold>Countervailing anti-inflammatory response and immunosuppression can cause death in late sepsis. Depletion and dysfunction of T cells are critical for developing sepsis-induced immunosuppression. Heme oxygenase-1 (HO-1) has a regulatory effect on differentiation and function of T cells and anti-inflammatory properties. We therefore investigated the immunosuppressive role of HO-1 in sepsis with a focus on its effects on helper T-cell (Th) differentiation and regulatory T cells (Treg).<bold>Methods: </bold>Sepsis was induced by cecal ligation and puncture (CLP). Mice were intraperitoneally injected with zinc protoporphyrin (ZnPP; 25 mg/kg), an HO-1 inhibitor, or hemin (20 mg/kg), an HO-1 inducer, at 24 and 36 hours post-CLP. Splenocytes were isolated 48 hours post-CLP. Mice were intranasally infected with Pseudomonas aeruginosa 4 days post-CLP as a secondary pneumonia infection model.<bold>Results: </bold>ZnPP improved survival and bacterial clearance, whereas hemin had the opposite effect in septic mice. CLP induced lymphocyte apoptosis and a proinflammatory Th1 to anti-inflammatory Th2 shift, which was attenuated by ZnPP. ZnPP attenuated the CLP-induced Treg population and protein expression of inhibitory costimulatory molecules. Furthermore, ZnPP improved survival in the secondary pneumonia infection model.<bold>Conclusions: </bold>Our findings suggest that HO-1 overexpression contributes to sepsis-induced immunosuppression during late phase sepsis by promoting Th2 polarization and Treg function.
- Subjects
SEPSIS; HEME oxygenase; IMMUNOSUPPRESSION; T cells; ANTI-inflammatory agents; HEMIN; ANIMALS; APOPTOSIS; MICE; OXIDOREDUCTASES; PORPHYRINS; PSEUDOMONAS; PSEUDOMONAS diseases; IMMUNOCOMPROMISED patients; CHEMICAL inhibitors
- Publication
Journal of Infectious Diseases, 2017, Vol 215, Issue 10, p1608
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jix142