TXNIP deficiency exacerbates endotoxic shock via the induction of excessive nitric oxide synthesis

Cited 47 time in scopus
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Title
TXNIP deficiency exacerbates endotoxic shock via the induction of excessive nitric oxide synthesis
Author(s)
Young-Jun ParkSung Jin Yoon; Hyun Woo Suh; Dongoh Kim; J R Park; Haiyoung JungTae-Don KimSuk Ran Yoon; Jeong Ki Min; Hee-Jun Na; Seon-Jin LeeHee Gu Lee; Y H Lee; H B Lee; In Pyo Choi
Bibliographic Citation
PLoS Pathogens, vol. 9, no. 10, pp. 1003646-1003646
Publication Year
2013
Abstract
Thioredoxin-interacting protein (TXNIP) has multiple functions, including tumor suppression and involvement in cell proliferation and apoptosis. However, its role in the inflammatory process remains unclear. In this report, we demonstrate that Txnip-/- mice are significantly more susceptible to lipopolysaccharide (LPS)-induced endotoxic shock. In response to LPS, Txnip-/- macrophages produced significantly higher levels of nitric oxide (NO) and inducible nitric oxide synthase (iNOS), and an iNOS inhibitor rescued Txnip-/- mice from endotoxic shock-induced death, demonstrating that NO is a major factor in TXNIP-mediated endotoxic shock. This susceptibility phenotype of Txnip-/- mice occurred despite reduced IL-1β secretion due to increased S-nitrosylation of NLRP3 compared to wild-type controls. Taken together, these data demonstrate that TXNIP is a novel molecule that links NO synthesis and NLRP3 inflammasome activation during endotoxic shock.
ISSN
1553-7366
Publisher
Public Library of Science
DOI
http://dx.doi.org/10.1371/journal.ppat.1003646
Type
Article
Appears in Collections:
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Aging Convergence Research Center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
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