| First Author | Park YJ | Year | 2013 |
| Journal | PLoS Pathog | Volume | 9 |
| Issue | 10 | Pages | e1003646 |
| PubMed ID | 24098117 | Mgi Jnum | J:245936 |
| Mgi Id | MGI:5914446 | Doi | 10.1371/journal.ppat.1003646 |
| Citation | Park YJ, et al. (2013) TXNIP deficiency exacerbates endotoxic shock via the induction of excessive nitric oxide synthesis. PLoS Pathog 9(10):e1003646 |
| abstractText | 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-1beta 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. |
