Evidence map›Paper›PMID 41805118›Full record

ArticleCNS neuroscience & therapeutics2026

IL-17A Promotes NETs Formation via the PKCζ-ERK-ROS-PAD4 Pathway in a Mouse Model of Ischemic Stroke.

Chang Liu, Qi Chen, Weijia Chen, Xinyue Han, Xiaowen Qiao, Jun Guo, Wei Su, Qingqing Dai

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. MMP8 Promotes NETosis in Gestational Diabetes Mellitus.Antioxidants (Basel, Switzerland) · 2026
    Article
  3. Review
  4. Review
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

8 authors.

Chang LiuDepartment of Geriatrics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Qi ChenDepartment of Geriatrics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Weijia ChenDepartment of Geriatrics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Xinyue HanDepartment of Geriatrics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Xiaowen QiaoDepartment of Geriatrics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Jun GuoDepartment of Geriatrics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Wei SuDepartment of Geriatrics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.ORCID 0000-0002-3284-7535
Qingqing DaiDepartment of Geriatrics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.ORCID 0009-0001-1987-0327

Funding

Beijing Tsinghua Changgung Hospital Fund 12025C01005National Natural Science Foundation of China 82101535The Beijing High-Level Innovation and Entrepreneurship Talent Support Program young backbone talent projects G202531272
6 · The paper itself

Abstract

aimsInterleukin-17A (IL-17A) aggravates poststroke neurological damage and enhances neutrophil extracellular traps (NETs) formation, yet the underlying mechanism remains unclear. This study aimed to elucidate how IL-17A regulates NETs generation after ischemic stroke.

methodsUsing a mouse middle cerebral artery occlusion (MCAO) model, we administered the Peptidylarginine deiminase 4 (PAD4) inhibitor GSK484 or an IL-17A-neutralizing antibody (IL-17mAb). Infarct volume and neurological function were assessed, and protein expression of PAD4, myeloperoxidase (MPO), citrullinated histones H3 (CitH3), protein kinase Cζ (PKCζ), and phosphorylated extracellular signal-regulated kinase (p-ERK) was evaluated. IL-17A

resultsInhibiting PAD4 with GSK484 can significantly reduce infarct size, improve neurological outcomes, and decrease PAD4, MPO, and CitH3 protein levels. Subsequently, we found that IL-17mAb treatment can reduce the expression of PAD4, MPO, and CitH3 in the peri-infarct area, as well as the expression of PKC-ζ and p-ERK. Similarly, the expression of PAD4 and CitH3 decreased in the peri-infarct area of IL-17A

conclusionIL-17A promotes NETs formation by upregulating PAD4 through the PKCζ-ERK-ROS pathway, exacerbating ischemic brain injury. Targeting this axis may offer a novel therapeutic strategy for stroke.

Indexed as

Extracellular TrapsInterleukin-17Ischemic StrokeMAP Kinase Signaling SystemProtein-Arginine Deiminase Type 4AnimalsDisease Models, AnimalExtracellular Signal-Regulated MAP KinasesInfarction, Middle Cerebral ArteryMaleMiceMice, Inbred C57BLMice, KnockoutProtein Kinase CProtein Kinase C zetaSignal TransductionExtracellular Signal-Regulated MAP KinasesIl17a protein, mouseInterleukin-17peptidylarginine deiminase 4, mouseProtein-Arginine Deiminase Type 4Protein Kinase CProtein Kinase C zetaIL‐17Aischemic strokeNETsPAD4

Identifiers

PMID41805118
PMCPMC12973334

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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.