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Title 

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

Authors 

Young-Jun ParkSeong Jin YoonHyun Woo SuhDongoh KimJ R ParkHaiyoung JungTae-Don KimSuk Ran YoonJeong Ki MinHee-Jun NaSeon-Jin LeeHee Gu LeeY H LeeH B LeeIn Pyo Choi

Publisher 

Public Library of Science

Issue Date 

2013

Citation 

Plos Pathogens, vol. 9, no. 10, pp. 1003646-1003646

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

Link 

http://dx.doi.org/10.1371/journal.ppat.1003646

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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