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IL-33 induces nuocytes and modulates liver injury in viral hepatitis.


ABSTRACT: Molecules containing damage-associated molecular patterns play an important role in many pathogenic processes. In this study, our aim was to investigate the role of IL-33, a damage-associated molecular pattern molecule, in adenovirus (Ad)-induced liver inflammation. Ad-infected mice exhibited a steadily increased IL-33 and its receptor IL-1R-like 1 expression in the liver during the first week of infection. Treatment of exogenous IL-33 resulted in a great decrease in the serum alanine aminotransferase levels and the number of Councilman bodies in the liver. Attenuated liver injury by IL-33 correlated with an increase in T regulatory cells but with a decrease in macrophages, dendritic cells, and NK cells in the liver. IL-33 enhanced both type 1 (IL-2 and IFN-?) and type 2 (IL-5 and IL-13) immune responses in infected mice. However, IL-33 inhibited TNF-? expression in hepatic T cells and macrophages, and significantly reduced TNF-? levels in the liver. We found that in addition to its direct effects, IL-33 strongly induced novel nuocytes in the livers and spleens of infected mice. When cocultured with nuocytes, hepatic T cells and macrophages expressed lower levels of TNF-?. The IL-33-treated mice also demonstrated a slight delay, but no significant impairment, in eliminating an intrahepatic infection with Ad. In conclusion, this study reveals that IL-33 acts as a potent immune stimulator and a hepatoprotective cytokine in acute viral hepatitis. Its direct immunoregulatory functions and ability to induce novel nuocytes further suggest to us that it may be a potentially promising therapeutic candidate for the management of viral hepatitis.

SUBMITTER: Liang Y 

PROVIDER: S-EPMC3660413 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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IL-33 induces nuocytes and modulates liver injury in viral hepatitis.

Liang Yuejin Y   Jie Zuliang Z   Hou Lifei L   Aguilar-Valenzuela Renan R   Vu David D   Soong Lynn L   Sun Jiaren J  

Journal of immunology (Baltimore, Md. : 1950) 20130429 11


Molecules containing damage-associated molecular patterns play an important role in many pathogenic processes. In this study, our aim was to investigate the role of IL-33, a damage-associated molecular pattern molecule, in adenovirus (Ad)-induced liver inflammation. Ad-infected mice exhibited a steadily increased IL-33 and its receptor IL-1R-like 1 expression in the liver during the first week of infection. Treatment of exogenous IL-33 resulted in a great decrease in the serum alanine aminotrans  ...[more]

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