Evidence map›Paper›PMID 37408199›Full record

ArticleCells2023

The RhoA-ROCK1/ROCK2 Pathway Exacerbates Inflammatory Signaling in Immortalized and Primary Microglia.

Elliot J Glotfelty, Luis B Tovar-Y-Romo, Shih-Chang Hsueh, David Tweedie, Yazhou Li, Brandon K Harvey, Barry J Hoffer, Tobias E Karlsson, Lars Olson, Nigel H Greig

Open access · goldAbstract read
In one paragraph

Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
5.5field-weighted citation impact, top 3% 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

39 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
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  9. Frontiers in pharmacology · 2026
    Article
  10. Review
  11. Article
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  17. Review
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  19. Translational andrology and urology · 2025
    Article
  20. Article
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

10 authors at 5 institutions in 3 countries.

Elliot J GlotfeltyDrug Design & Development Section, Translational Gerontology Branch, Intramural Research Program National Institute on Aging, NIH, Baltimore, MD 21224, USA.ORCID 0000-0001-5125-8720
Luis B Tovar-Y-RomoDivision of Neuroscience, Institute of Cellular Physiology, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.ORCID 0000-0003-2605-1378
Shih-Chang HsuehDrug Design & Development Section, Translational Gerontology Branch, Intramural Research Program National Institute on Aging, NIH, Baltimore, MD 21224, USA.
David TweedieDrug Design & Development Section, Translational Gerontology Branch, Intramural Research Program National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Yazhou LiDrug Design & Development Section, Translational Gerontology Branch, Intramural Research Program National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Brandon K HarveyMolecular Mechanisms of Cellular Stress and Inflammation Unit, Integrative Neuroscience Department, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Barry J HofferDepartment of Neurosurgery, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Tobias E KarlssonDepartment of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
Lars OlsonDepartment of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.ORCID 0000-0001-7378-7420
Nigel H GreigDrug Design & Development Section, Translational Gerontology Branch, Intramural Research Program National Institute on Aging, NIH, Baltimore, MD 21224, USA.ORCID 0000-0002-3032-1468
National Institute on Aging · USKarolinska Institutet · SENational Institutes of Health · USUniversidad Nacional Autónoma de México · MXUniversity School · US

Funding

Pro-inflammatory cytokine lowering anti-inflammatory drugsZIAAG000994 · NIA · NATIONAL INSTITUTE ON AGING · PI GREIG, NIGEL H. · 2016 to 2025
$16.8M
Eating Behaviors in Homebound Older AdultsK01AG000994 · NIA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LOCHER, JULIE L · 2001 to 2005
$503k
NIA NIH HHS K01 AG000994NIH HHS AG00000994
6 · The paper itself

Abstract

Neuroinflammation is a unifying factor among all acute central nervous system (CNS) injuries and chronic neurodegenerative disorders. Here, we used immortalized microglial (IMG) cells and primary microglia (PMg) to understand the roles of the GTPase Ras homolog gene family member A (RhoA) and its downstream targets Rho-associated coiled-coil-containing protein kinases 1 and 2 (ROCK1 and ROCK2) in neuroinflammation. We used a pan-kinase inhibitor (Y27632) and a ROCK1- and ROCK2-specific inhibitor (RKI1447) to mitigate a lipopolysaccharide (LPS) challenge. In both the IMG cells and PMg, each drug significantly inhibited pro-inflammatory protein production detected in media (TNF-α, IL-6, KC/GRO, and IL-12p70). In the IMG cells, this resulted from the inhibition of NF-κB nuclear translocation and the blocking of neuroinflammatory gene transcription (iNOS, TNF-α, and IL-6). Additionally, we demonstrated the ability of both compounds to block the dephosphorylation and activation of cofilin. In the IMG cells, RhoA activation with Nogo-P4 or narciclasine (Narc) exacerbated the inflammatory response to the LPS challenge. We utilized a siRNA approach to differentiate ROCK1 and ROCK2 activity during the LPS challenges and showed that the blockade of both proteins may mediate the anti-inflammatory effects of Y27632 and RKI1447. Using previously published data, we show that genes in the RhoA/ROCK signaling cascade are highly upregulated in the neurodegenerative microglia (MGnD) from APP/PS-1 transgenic Alzheimer's disease (AD) mice. In addition to illuminating the specific roles of RhoA/ROCK signaling in neuroinflammation, we demonstrate the utility of using IMG cells as a model for primary microglia in cellular studies.

Indexed as

MicrogliaTumor Necrosis Factor-alphaAmidesAnimalsInterleukin-6LipopolysaccharidesMiceMice, TransgenicNeuroinflammatory DiseasesPyridinesAmidesInterleukin-6LipopolysaccharidesPyridinesTumor Necrosis Factor-alphaY 27632microglianeuroinflammationNF-κBRhoAROCK1ROCK2ROCK inhibitors

Identifiers

PMID37408199
PMCPMC10216802
OpenAlexW4376279785

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.