Evidence map›Paper›PMID 34235623›Full record

ArticleImmunologic research2021

TLR4 and TNFR1 blockade dampen M1 macrophage activation and shifts them towards an M2 phenotype.

Ritasha Sawoo, Rajen Dey, Rituparna Ghosh, Biswadev Bishayi

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In one paragraph

Article in Immunologic research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 9% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. Lipopolysaccharide-mediated macrophage polarization, conserved pathogenesis, and implications for peripheral neuropathy: a systematic review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Pooled it
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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

4 authors at 1 institution in 1 country.

Ritasha SawooDepartment of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, 92 APC Road, Calcutta, 700009, West Bengal, India.
Rajen DeyDepartment of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, 92 APC Road, Calcutta, 700009, West Bengal, India.
Rituparna GhoshDepartment of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, 92 APC Road, Calcutta, 700009, West Bengal, India.
Biswadev BishayiDepartment of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, 92 APC Road, Calcutta, 700009, West Bengal, India. biswadevbishayi4@gmail.com.ORCID http://orcid.org/0000-0001-8603-8621
University of Calcutta · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Gram-negative bacterial lipopolysaccharide (LPS)-induced sepsis has emerged as major concern worldwide due to the pressing need to develop its effective treatment strategies which is not available yet. LPS is the major causative agent in the pathogenesis of septic shock. In macrophages, LPS interacts with cell surface TLR4 leading to reactive oxygen species (ROS), TNF-α, IL-1β production, oxidative stress and markedly activated the MAPKs and NF-kB pathway. Post cell isolation, the macrophages were subjected to administration with neutralizing antibodies to TLR4 and TNFR1 either alone or in combination prior to LPS challenge. Subsequently, we performed flow cytometric analysis along with Western blots, reactive oxygen species production, and TNF-α, IL-1β release. Outcomes suggested that the dual blockade of TLR4 and TNFR1 was indeed beneficial in shifting the LPS-induced M1 polarization towards M2. Both TLR4 and TNFR1 exhibited dependency during LPS stimulation. Furthermore, the switch towards the M2 phenotype might be responsible for the decreased levels of TNF-α, IL-1β, NO, and superoxide anion and the simultaneous elevation in the activity level of anti-oxidant enzymes like SOD, CAT (catalase), and GSH content in the isolated peritoneal macrophages. Simultaneous blocking of both TLR4 and TNFR1 also showed reduced expression of NF-kB, JNK, and COX-2 by promoting TNFR2-mediated TNF-α signaling. The increased arginase activity further confirmed the polarization towards M2. Thus it may be inferred that dual blockade of TLR4 and TNFR1 might be an alternative therapeutic approach for regulating of sepsis in future.

Indexed as

AnimalsAntibodies, NeutralizingArginaseFree RadicalsGlutathioneInterleukin-1betaLipopolysaccharidesMacrophage ActivationMacrophages, PeritonealMaleMiceOxidoreductasesPhenotypeReceptors, ImmunologicTumor Necrosis Factor-alphaAntibodies, NeutralizingArginaseFree RadicalsGlutathioneIL1B protein, mouseInterleukin-1betaLipopolysaccharidesOxidoreductasesReceptors, ImmunologicTnf protein, mouseTumor Necrosis Factor-alphaInflammationLPSM1/M2 polarizationMacrophageTLR4TNFR1

Identifiers

PMID34235623
OpenAlexW3179444984

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.