TXNIP Deficiency Exacerbates Endotoxic Shock via the Induction of Excessive Nitric Oxide Synthesis e1003646

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 lipo...

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Published inPLoS pathogens Vol. 9; no. 10
Main Authors Park, Young-Jun, Yoon, Sung-Jin, Suh, Hyun-Woo, Kim, Dong Oh, Park, Jeong-Ran, Jung, Haiyoung, Kim, Tae-Don, Yoon, Suk Ran, Min, Jeong-Ki, Na, Hee-Jun, Lee, Seon-Jin, Lee, Hee Gu, Lee, Young Ho, Lee, Hee-Bong, Choi, Inpyo
Format Journal Article
LanguageEnglish
Published San Francisco Public Library of Science 01.10.2013
Subjects
Apoptosis
Cell growth
E coli
Experiments
Nitric oxide
Proteins
Regulation
Rodents
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Summary: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
1553-7374
DOI:10.1371/journal.ppat.1003646