Phosphatase PTP1B negatively regulates MyD88- and TRIF-dependent proinflammatory cytokine and type I interferon production in TLR-triggered macrophages

Xu, Hongmei; An, Huazhang; Hou, Jin; Han, Chaofeng; Wang, Pin; Yu, Yizhi; Cao, Xuetao

doi:10.1016/j.molimm.2008.05.006

Cited by 84 publications

(83 citation statements)

References 43 publications

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“…1B). As a parallel control, TLR4/3-and RIG-I-induced NF-kB activation was greatly inhibited by PTP1B, which was consistent with a previous report (21).…”

Section: Ptpn4 Negatively Regulates Tlr4-induced Ifn-b Productionsupporting

confidence: 92%

“…However, the phosphorylation modification of key proteins in PRRs signaling has not been fully elucidated. Protein tyrosine phosphatases (PTPs), which dephosphorylate tyrosine residues of target substrates (15,16), have been reported to be involved in the regulation of innate immune responses, such as Src homology region 2 domain-containing phosphatase-1 (17), Src homology region 2 domain-containing phosphatase-2 (18), PTPN22 (19), PTP with proline-glutamine-serine-threonine-rich motifs (20), PTP1B (21), and so on. However, the PTPs identified to be PRRs regulators possessed broadly regulatory effects and that limited their potential implication for immunotherapy.…”

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confidence: 99%

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Phosphatase PTPN4 Preferentially Inhibits TRIF-Dependent TLR4 Pathway by Dephosphorylating TRAM

Huai

Song

Wang

et al. 2015

The Journal of Immunology

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TLR4 recruits TRIF-related adaptor molecule (TRAM, also known as TICAM2) as a sorting adaptor to facilitate the interaction between TLR4 and TRIF and then initiate TRIF-dependent IRF3 activation. However, the mechanisms by which TRAM links downstream molecules are not fully elucidated. In this study, we show that TRAM undergoes tyrosine phosphorylation upon TLR4 activation and that is required for TLR4-induced IRF3 activation. Protein tyrosine phosphatase nonreceptor type 4 (PTPN4), a protein tyrosine phosphatase, inhibits tyrosine phosphorylation and subsequent cytoplasm translocation of TRAM, resulting in the disturbance of TRAM–TRIF interaction. Consequently, PTPN4 specifically inhibits TRIF-dependent IRF3 activation and IFN-β production in TLR4 pathway. Therefore, our results provide new insight into the TLR4 pathway and identify PTPN4 as a specific inhibitor of TRIF-dependent TLR4 pathway. Targeting PTPN4 would be beneficial for the development of new strategy to control TLR4-associated diseases without unwanted side effects.

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“…1B). As a parallel control, TLR4/3-and RIG-I-induced NF-kB activation was greatly inhibited by PTP1B, which was consistent with a previous report (21).…”

Section: Ptpn4 Negatively Regulates Tlr4-induced Ifn-b Productionsupporting

confidence: 92%

mentioning

confidence: 99%

Phosphatase PTPN4 Preferentially Inhibits TRIF-Dependent TLR4 Pathway by Dephosphorylating TRAM

Huai

Song

Wang

et al. 2015

The Journal of Immunology

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“…4,5 Moreover, any dysregulation of this process has been associated with inflammatory diseases, autoimmune diseases or pathogen dissemination. Many molecules have been identified as positive or negative regulators of TLR signaling, 6,7 including phosphatases (SHP-1, SHP-2, SHIP-1, PTP1B, [8][9][10][11] etc. ), protein kinases (calmodulin-dependent protein kinase II, Btk, MEKK3, [12][13][14] etc.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs in the regulation of TLR and RIG-I pathways

2012

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The innate immune system recognizes invading pathogens through germline-encoded pattern recognition receptors (PRRs), which elicit innate antimicrobial and inflammatory responses and initiate adaptive immunity to control or eliminate infection. Toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I) are the key innate immune PRRs and are tightly regulated by elaborate mechanisms to ensure a beneficial outcome in response to foreign invaders. Although much of the focus in the literature has been on the study of protein regulators of inflammation, microRNAs (miRNAs) have emerged as important controllers of certain features of the inflammatory process. Several miRNAs are induced by TLR and RIG-I activation in myeloid cells and act as feedback regulators of TLR and RIG-I signaling. In this review, we comprehensively discuss the recent understanding of how miRNA networks respond to TLR and RIG-I signaling and their role in the initiation and termination of inflammatory responses. Increasing evidence also indicates that both virus-encoded miRNAs and cellular miRNAs have important functions in viral replication and host anti-viral immunity.

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“…Knockdown of PTP1B increases production of TNFA and IL-6 in TLR-triggered macrophages. 46 In addition, PTP1B deficient macrophages display increased inflammatory activity in vitro and in vivo. 47 Moreover, PTP1B deficiency exacerbates inflammation and accelerates leukocyte trafficking in vivo.…”

Section: Discussionmentioning

confidence: 99%

Pancreatic Protein Tyrosine Phosphatase 1B Deficiency Exacerbates Acute Pancreatitis in Mice

Bettaieb

Koike

Chahed

et al. 2016

The American Journal of Pathology

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Acute pancreatitis (AP) is a common and devastating gastrointestinal disorder that causes significant morbidity. The disease starts as local inflammation in the pancreas that may progress to systemic inflammation and complications. Protein tyrosine phosphatase 1B (PTP1B) is implicated in inflammatory signaling, but its significance in AP remains unclear. To investigate whether PTP1B may have a role in AP, we used pancreas PTP1B knockout (panc-PTP1B KO) mice and determined the effects of pancreatic PTP1B deficiency on cerulein-and arginine-induced acute pancreatitis. We report that PTP1B protein expression was increased in the early phase of AP in mice and rats. In addition, histological analyses of pancreas samples revealed enhanced features of AP in cerulein-treated panc-PTP1B KO mice compared with controls. Moreover, cerulein-and arginine-induced serum amylase and lipase were significantly higher in panc-PTP1B KO mice compared with controls. Similarly, pancreatic mRNA and serum concentrations of the inflammatory cytokines IL-1B, IL-6, and tumor necrosis factor-a were increased in panc-PTP1B KO mice compared with controls. Furthermore, panc-PTP1B KO mice exhibited enhanced cerulein-and arginine-induced NF-kB inflammatory response accompanied with increased mitogen-activated protein kinases activation and elevated endoplasmic reticulum stress. Notably, these effects were recapitulated in acinar cells treated with a pharmacological inhibitor of PTP1B. These findings reveal a novel role for pancreatic PTP1B in cerulein-and arginine-induced acute pancreatitis. (Am J Pathol 2016 http://dx

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Phosphatase PTP1B negatively regulates MyD88- and TRIF-dependent proinflammatory cytokine and type I interferon production in TLR-triggered macrophages

Cited by 84 publications

References 43 publications

Phosphatase PTPN4 Preferentially Inhibits TRIF-Dependent TLR4 Pathway by Dephosphorylating TRAM

Phosphatase PTPN4 Preferentially Inhibits TRIF-Dependent TLR4 Pathway by Dephosphorylating TRAM

MicroRNAs in the regulation of TLR and RIG-I pathways

Pancreatic Protein Tyrosine Phosphatase 1B Deficiency Exacerbates Acute Pancreatitis in Mice

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