Evidence mapPaperPMID 39862276Full record

ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2025

Pericytes mediate neuroinflammation via Fli-1 in endotoxemia and sepsis in mice.

Pengfei Li, Liu Liu, Perry V Halushka, Maria Trojanowska, Guirong Wang, Adviye Ergul, Hongkuan Fan

Abstract read
In one paragraph

Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

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

3 citing papers in PubMed.

  1. Article
  2. Chemogenetic modulation of CNS pericytes: Impact on pericyte CaMolecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  3. 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

7 authors.

Pengfei LiDepartment of Pathology and Laboratory Medicine, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC, 29425, USA.
Liu LiuDepartment of Pathology and Laboratory Medicine, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC, 29425, USA.
Perry V HalushkaDepartment of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA.
Maria TrojanowskaArthritis and Autoimmune Diseases Center, Boston University, Boston, MA, 02118, USA.
Guirong WangDepartments of Surgery and Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
Adviye ErgulDepartment of Pathology and Laboratory Medicine, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC, 29425, USA.
Hongkuan FanDepartment of Pathology and Laboratory Medicine, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC, 29425, USA. fanhong@musc.edu.

Funding

The Role of Pericytes in Brain Hypoperfusion in Alzheimer's Disease DevelopmentR01AG081807 · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2025 to 2025
$608k
The Role of Pericytes in the Vascular Dysfunction of SepsisR35GM149203 · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2025 to 2025
$378k
BLRD VA I01 BX000347BLRD VA IK6 BX004471NCATS NIH HHS UL1 TR001450NIA NIH HHS R01 AG081807NIGMS NIH HHS R35 GM149203NINDS NIH HHS RF1 NS083559NINDS NIH HHS RF1 NS104573
6 · The paper itself

Abstract

backgroundSepsis-associated encephalopathy (SAE) often results from neuroinflammation. Recent studies have shown that brain platelet-derived growth factor receptor β (PDGFRβ) cells, including pericytes, may act as early sensors of infection by secreting monocyte chemoattractant protein-1 (MCP-1), which transmits inflammatory signals to the central nervous system. The erythroblast transformation-specific (ETS) transcription factor Friend leukemia virus integration 1 (Fli-1) plays a critical role in inflammation by regulating the expression of key cytokines, including MCP-1. However, the role of pericyte Fli-1 in neuroinflammation during sepsis remains largely unknown.

methodsWT and pericyte-specific Fli-1 knockout mice were subjected to endotoxemia through LPS injection or sepsis via cecal ligation and puncture (CLP). In vitro, Fli-1 was knocked down using small interfering RNA in cultured mouse brain pericytes, followed by LPS stimulation.

resultsElevated Fli-1 levels were observed in isolated brain pericytes 2 h after LPS administration, in brain tissues 4 h after CLP, and in cultured mouse brain pericytes 2 h after LPS stimulation in vitro. In endotoxemic mice, pericyte-specific Fli-1 knockout reduced expression of MCP-1 and IL-6 in brain tissue 2 h after LPS injection. At 24 h post-LPS administration, protein levels of MCP-1 and IL-6, and microglia activation were suppressed in pericyte-Fli-1 knockout mice. Additionally, Fli-1 deficiency in pericytes significantly reduced MCP-1 and IL-6 mRNA levels in the brain tissue 4 h after CLP. Moreover, in cultured brain pericytes, Fli-1 knockdown markedly decreased MCP-1 and IL-6 levels after LPS stimulation. Notably, LPS stimulation increased Fli-1 levels via TLR4-Myd88 signaling, which subsequently led to elevated production of MCP-1 in brain pericytes.

conclusionsFli-1 in pericytes may serve as a crucial mediator of neuroinflammation during sepsis by directly regulating pivotal cytokines such as MCP-1 and IL-6. Therefore, Fli-1 has the potential to serve as a therapeutic target in SAE and other neuroinflammatory disorders.

Indexed as

EndotoxemiaNeuroinflammatory DiseasesPericytesProto-Oncogene Protein c-fli-1SepsisAnimalsBrainCells, CulturedChemokine CCL2LipopolysaccharidesMaleMiceMice, Inbred C57BLMice, KnockoutChemokine CCL2Fli1 protein, mouseLipopolysaccharidesProto-Oncogene Protein c-fli-1Fli-1NeuroinflammationPericytesSepsis

Identifiers

PMID39862276
PMCPMC11762421

What Socratic 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 Socratic graph.