Evidence map›Paper›PMID 26324446›Full record

ArticleThe Journal of experimental medicine2015

NOS1-derived nitric oxide promotes NF-κB transcriptional activity through inhibition of suppressor of cytokine signaling-1.

Mirza Saqib Baig, Sofia V Zaichick, Mao Mao, Andre L de Abreu, Farnaz R Bakhshi, Peter C Hart, Uzma Saqib, Jing Deng, Saurabh Chatterjee, Michelle L Block and 7 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
4.0field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

59 citing papers in PubMed, 108 citations in OpenAlex.

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  16. Localized cytotoxic T cell-associated antigen 4 and antioxidant islet encapsulation alters macrophage signaling and induces regulatory and anergic T cells to enhance allograft survival.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2023
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  17. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 5 institutions in 2 countries.

Mirza Saqib BaigDepartment of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607 Department of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607.
Sofia V ZaichickDepartment of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607 Department of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607.
Mao MaoDepartment of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607 Department of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607.
Andre L de AbreuDepartment of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607 Department of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607 Programa de Biociencias Aplicadas a Farmacia (PBF), Universidade Estadual de Maringa, Maringa 87020-900, Brazil.
Farnaz R BakhshiDepartment of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607.
Peter C HartDepartment of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607 Department of Anatomy and Cell Biology, Stark Neurosciences Research Institute, Indiana University, Indianapolis, IN 46202.
Uzma SaqibDepartment of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607.
Jing DengDepartment of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607.
Saurabh ChatterjeeDepartment of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607.
Michelle L BlockDepartment of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607.
Stephen M VogelDepartment of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607.
Asrar B MalikDepartment of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607.
Marcia E L ConsolaroPrograma de Biociencias Aplicadas a Farmacia (PBF), Universidade Estadual de Maringa, Maringa 87020-900, Brazil.
John W ChristmanDepartment of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607.
Richard D MinshallDepartment of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607 Department of Environmental Health Sciences, University of South Carolina, Columbia, SC 29208.
Benjamin N GantnerDepartment of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607 mbonini@uic.edu bgantner@uic.edu.
Marcelo G BoniniDepartment of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607 Department of Medicine, Department of Pharmacology, Department of Anesthesiology, and Department of Pathology, University of Illinois College of Medicine, Chicago, IL 60607 Department of Anatomy and Cell Biology, Stark Neurosciences Research Institute, Indiana University, Indianapolis, IN 46202 mbonini@uic.edu bgantner@uic.edu.
Illinois College · USUniversity of Illinois Urbana-Champaign · USIndiana University – Purdue University Indianapolis · USUniversidade Estadual de Maringá · BRUniversity of Illinois Chicago · US

Funding

Trpm2 Regulation of Phagocyte Bactericidal Activity and Resolution of Lung InjuryP01HL077806 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI ZHAO, YOU-YANG · 2005 to 2019
$27.0M
Macrophage Gene Expression in Acute Lung InflammationR01HL075557 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI CHRISTMAN, JOHN W · 2004 to 2016
$4.8M
New Strategies for Treating Septic Vasculopathy Inflammation and ThrombosisR01HL125356 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI BONINI, MARCELO G., DU, XIAOPING · 2014 to 2018
$3.4M
Repair mechanisms of sepsis induced endothelial dysfunction and lung injuryR01HL125350 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MALIK, ASRAR B., ZHAO, YOU-YANG · 2014 to 2018
$3.2M
NHLBI NIH HHS P01 HL077806NHLBI NIH HHS R01 HL075557NHLBI NIH HHS R01 HL125350NHLBI NIH HHS R01 HL125356
6 · The paper itself

Abstract

The NF-κB pathway is central to the regulation of inflammation. Here, we demonstrate that the low-output nitric oxide (NO) synthase 1 (NOS1 or nNOS) plays a critical role in the inflammatory response by promoting the activity of NF-κB. Specifically, NOS1-derived NO production in macrophages leads to proteolysis of suppressor of cytokine signaling 1 (SOCS1), alleviating its repression of NF-κB transcriptional activity. As a result, NOS1(-/-) mice demonstrate reduced cytokine production, lung injury, and mortality when subjected to two different models of sepsis. Isolated NOS1(-/-) macrophages demonstrate similar defects in proinflammatory transcription on challenge with Gram-negative bacterial LPS. Consistently, we found that activated NOS1(-/-) macrophages contain increased SOCS1 protein and decreased levels of p65 protein compared with wild-type cells. NOS1-dependent S-nitrosation of SOCS1 impairs its binding to p65 and targets SOCS1 for proteolysis. Treatment of NOS1(-/-) cells with exogenous NO rescues both SOCS1 degradation and stabilization of p65 protein. Point mutation analysis demonstrated that both Cys147 and Cys179 on SOCS1 are required for its NO-dependent degradation. These findings demonstrate a fundamental role for NOS1-derived NO in regulating TLR4-mediated inflammatory gene transcription, as well as the intensity and duration of the resulting host immune response.

Indexed as

AnimalsCytokinesHumansLipopolysaccharidesMacrophagesMice, Inbred C57BLMice, KnockoutMice, TransgenicMolecular Sequence DataNF-kappa BNitric OxideNitric Oxide Synthase Type INitric Oxide Synthase Type IINitric Oxide Synthase Type IIISepsisSuppressor of Cytokine Signaling 1 ProteinCytokinesLipopolysaccharidesNF-kappa BNitric OxideNitric Oxide Synthase Type INitric Oxide Synthase Type IINitric Oxide Synthase Type IIINos1 protein, mouseNos2 protein, mouseNos3 protein, mouseSocs1 protein, mouseSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling ProteinsTlr4 protein, mouseToll-Like Receptor 4

Identifiers

PMID26324446
PMCPMC4577833
OpenAlexW1911986360

What Socratic holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.