Phosphatase SHP-1 promotes TLR- and RIG-I-activated production of type I interferon by inhibiting the kinase IRAK1

An, Huazhang; Hou, Jin; Zhou, Jun; Zhao, Wei; Xu, Hongmei; Zheng, Yuejuan; Yu, Yizhi; Liu, Shuxun; Cao, Xuetao

doi:10.1038/ni.1604

Cited by 229 publications

(201 citation statements)

References 35 publications

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“…The separated proteins were next transferred onto nitrocellulose membranes, and then analyzed by Western blotting as previously described. 31 Flow cytometry Anti-CD4-PE, anti-CD25-FITC, anti-CD4-FITC, anti-IL-17A-PE, anti-Foxp3-PE, anti-CTLA4-APC, Annexin V-FITC and CFSE were purchased from either eBiosciences or BioLegend. Intracellular stainings for FOXP3, CTLA-4 and IL-17A were performed using the relevent Fix/Perm Buffer set as instructed.…”

Section: Western Blot Analysismentioning

confidence: 99%

SAHA, an HDAC inhibitor, synergizes with tacrolimus to prevent murine cardiac allograft rejection

et al. 2012

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Suberoylanilide hydroxamic acid (SAHA), as a histone deacetylase (HDAC) inhibitor (HDACi), was recently found to exhibit an immunosuppressive effect. However, whether SAHA can synergize with calcineurin inhibitors (CNIs) to inhibit allograft rejection and its underlying mechanism remain elusive. In this study, we demonstrated the synergistic effects of SAHA and non-therapeutic dose of tacrolimus (FK506) in prolonging the allograft survival in a murine cardiac transplant model. Concomitant intragraft examination revealed that allografts from SAHA-treated recipients showed significantly lower levels of IL-17 expression, and no discernable difference for IL-17 expressions was detected between SAHA-and SAHA/FK506-treated allograft as compared with allografts from FK506-treated animals. In contrast, administration of FK506 significantly suppressed interferon (IFN)-c but increased IL-10 expression as compared with that of SAHA-treated animals, and this effect was independent of SAHA. Interestingly, SAHA synergizes with FK506 to promote Foxp3 and CTLA4 expression. In vitro, SAHA reduced the proportion of Th17 cells in isolated CD4 1 T-cell population and decreased expressions of IL-17A, IL-17F, STAT3 and RORct in these cells. Moreover, SAHA enhances suppressive function of regulatory T (Treg) cells by upregulating the expression of CTLA-4 without affecting T effector cell proliferation, and increased the proportion of Treg by selectively promoting apoptosis of T effector cells. Therefore, SAHA, a HDACi, may be a promising immunosuppressive agent with potential benefit in conjunction with CNI drugs.

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Section: Western Blot Analysismentioning

confidence: 99%

SAHA, an HDAC inhibitor, synergizes with tacrolimus to prevent murine cardiac allograft rejection

et al. 2012

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“…Dual-luciferase reporter assay RAW264.7 cells were co-transfected with the mixture of 100 ng pGL3.5×κB-luciferase reporter plasmid, 10 ng pRL-TKRenilla-luciferase plasmid using Lipofectimine TM 2000 Reagent (Invitrogen, Carlsbad, CA) as described previously by us (11). Forty-eight hours after transfection, cells were left untreated or treated with indicated concentrations of albaconol.…”

Section: Rt-pcr Analysis Of Cytokine Expressionmentioning

confidence: 99%

Albaconol, a Plant-Derived Small Molecule, Inhibits Macrophage Function by Suppressing NF-κB Activation and Enhancing SOCS1 Expression

et al. 2008

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Discovery and functional identification of plant-derived small compounds as the immunosuppressant attract much attention these years. Albaconol is a new kind of small compound, prenylated resorcinol, isolated from the fruiting bodies of the inedible mushroom Albatrellus confluens. Our previous studies showed that albaconol can inhibit tumor cell growth and dendritic cell maturation. However, the immunomodulatory roles and the underlying mechanisms of albaconol have not been fully understood. In this study we investigated the effects of albaconol on the proliferation and LPS-induced proinflammatory cytokine production of macrophages. Albaconol, when used at a dose higher than 1.0 μg/ml, inhibited proliferation of RAW264.7 cells in a dose-and time-dependent manner, and could induce cellular apoptosis when used at high dosage (≥ 7.5 μg/ml). Furthermore, we found that albaconol used at a lower dosage without apoptosis induction could significantly inhibit LPS-induced TNF-α, IL-6, IL-1β and NO production in RAW264.

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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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Phosphatase SHP-1 promotes TLR- and RIG-I-activated production of type I interferon by inhibiting the kinase IRAK1

Cited by 229 publications

References 35 publications

SAHA, an HDAC inhibitor, synergizes with tacrolimus to prevent murine cardiac allograft rejection

SAHA, an HDAC inhibitor, synergizes with tacrolimus to prevent murine cardiac allograft rejection

Albaconol, a Plant-Derived Small Molecule, Inhibits Macrophage Function by Suppressing NF-κB Activation and Enhancing SOCS1 Expression

MicroRNAs in the regulation of TLR and RIG-I pathways

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