Roles of peroxiredoxin II in the regulation of proinflammatory responses to LPS and protection against endotoxin-induced lethal shock

Yang, Chul–Su; Lee, Dong‐Seok; Song, Chang‐Hwa; An, Se-Jin; Li, Shengjin; Kim, Jin Man; Kim, Cuk-Seong; Yoo, Dae Goon; Jeon, Byeong Hwa; Yang, Hee‐Young; Lee, Tae‐Hoon; Lee, Zee-Won; El-Benna, Jamel; Yu, Dae‐Yeul; Jo, Eun-Kyeong

doi:10.1084/jem.20061849041807c

Cited by 2 publications

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“…The stimulation of TLR4 by its cognate ligands leads to the induction of cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) as well as the production of NO in RAW264.7 cells [25,48]. Moreover, it has been reported that stimulation of primary macrophages by LPS is responsible for the induction of both mitochondrial and intracellular formation of ROS [49,50]. Our data revealed that TIP3 successfully represses the LPS-induced extracellular secretion of NO and the expression of iNOS and COX2 in a dose-dependent manner (Fig.…”

Section: Tip3 Inhibits Myd88-dependent and -Independent Tlr4 And Tlr3 Signalling In Macrophagesmentioning

confidence: 99%

A peptide derived from the core β-sheet region of TIRAP decoys TLR4 and reduces inflammatory and autoimmune symptoms in murine models

et al. 2020

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Background: TLRs are some of the actively pursued drug-targets in immune disorders. Owing to a recent surge in the cognizance of TLR structural biology and signalling pathways, numerous therapeutic modulators, ranging from low-molecular-weight organic compounds to polypeptides and nucleic acid agents have been developed.Methods: A penetratin-conjugated small peptide (TIP3), derived from the core b-sheet of TIRAP, was evaluated in vitro by monitoring the TLR-mediated cytokine induction and quantifying the protein expression using western blot. The therapeutic potential of TIP3 was further evaluated in TLR-dependent in vivo disease models. Findings: TIP3 blocks the TLR4-mediated cytokine production through both the MyD88-and TRIF-dependent pathways. A similar inhibitory-effect was exhibited for TLR3 but not on other TLRs. A profound therapeutic effect was observed in vivo, where TIP3 successfully alleviated the inflammatory response in mice model of collagen-induced arthritis and ameliorated the disease symptoms in psoriasis and SLE models. Interpretation: Our data suggest that TIP3 may be a potential lead candidate for the development of effective therapeutics against TLR-mediated autoimmune disorders.

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Section: Tip3 Inhibits Myd88-dependent and -Independent Tlr4 And Tlr3 Signalling In Macrophagesmentioning

confidence: 99%

A peptide derived from the core β-sheet region of TIRAP decoys TLR4 and reduces inflammatory and autoimmune symptoms in murine models

et al. 2020

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Deletion of peroxiredoxin 6 potentiates lipopolysaccharide-induced acute lung injury in mice*

Yang

Song

Wang

et al. 2011

Critical Care Medicine

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Peroxiredoxin 6 (PRDX6) is a member of the PRDX family of antioxidant enzymes and correlated with inflammatory response. Therefore, we investigated the role of PRDX6 during lipopolysaccharide (LPS)-induced acute kidney injury. Both 3 months aged PRDX6-overexpressing transgenic mice (PRDX6 mice) and wild type (WT) mice had acute renal injury induced by intraperitoneal injection of LPS (10 mg/kg)., PRDX6 mice showed decreased mortality and renal injury following LPS challenge compared to WT mice. Furthermore, infiltration of macrophages, T-cells and neutrophils, and the number of apoptotic cells were more decreased by LPS treatment in PRDX6 mice than in WT mice. Because LPS induces reactive oxygen species (ROS) production which induces inflammation through c-Jun N-terminal Kinase (JNK) and p38 MAPK activation, we investigated ROS concentration and MAPK signaling pathway in the kidney of PRDX6 mice. As expected, LPS-induced oxidative stress was attenuated, and p38 MAPK and JNK activation was decreased in the kidney of PRDX6 mice. Inhibitory effect of PRDX6 on LPS-induced apoptosis and MAPK activation in the primary renal proximal tubular cells were overcome by treatment with PRDX6 inhibitor or hydrogen peroxide. These results suggest that PRDX6 overexpression inactivates p38 MAPK and JNK pathway through decrease LPS-induced ROS concentration in the kidney, resulting in inhibition of renal apoptosis and leukocyte infiltration and led to attenuation of LPS-induced acute kidney injury.

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Roles of peroxiredoxin II in the regulation of proinflammatory responses to LPS and protection against endotoxin-induced lethal shock

Cited by 2 publications

References 0 publications

A peptide derived from the core β-sheet region of TIRAP decoys TLR4 and reduces inflammatory and autoimmune symptoms in murine models

A peptide derived from the core β-sheet region of TIRAP decoys TLR4 and reduces inflammatory and autoimmune symptoms in murine models

Deletion of peroxiredoxin 6 potentiates lipopolysaccharide-induced acute lung injury in mice*

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