Evidence map›Paper›PMID 25589066›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2015

High-mobility group box 1: a novel target for treatment of Pseudomonas aeruginosa keratitis.

Sharon McClellan, Xiaoyu Jiang, Ronald Barrett, Linda D Hazlett

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.2field-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

24 citing papers in PubMed, 32 citations in OpenAlex.

  1. Review
  2. Article
  3. Glycyrrhizin Interacts with TLR4 and TLR9 to ResolvePathogens (Basel, Switzerland) · 2022
    Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. HMGB1 Antagonist, Box A, Reduces TLR4, RAGE, and Inflammatory Cytokines in the Cornea of P. aeruginosa-Infected Mice.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2018
    Article
  12. Topical Glycyrrhizin Is Therapeutic for Pseudomonas aeruginosa Keratitis.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2018
    Article
  13. High-Mobility Group Box 1 in Dry Eye Inflammation.Investigative ophthalmology & visual science · 2018
    Article
  14. Review
  15. Article
  16. Article
  17. Emerging role of HMGB1 in lung diseases: friend or foe.Journal of cellular and molecular medicine · 2017
    Review
  18. Article
  19. Article
  20. Challenges of corneal infections.Expert review of ophthalmology · 2016
    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

4 authors at 1 institution in 1 country.

Sharon McClellanDepartment of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201.
Xiaoyu JiangDepartment of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201.
Ronald BarrettDepartment of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201.
Linda D HazlettDepartment of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201 lhazlett@med.wayne.edu.
Wayne State University · US

Funding

VISION RESEARCH--COREP30EY004068 · NEI · WAYNE STATE UNIVERSITY · PI LINDA D HAZLETT · 1985 to 2026
$13.2M
ALTERATION WITH AGE OF RESISTANCE TO EYE INFECTIONSR01EY002986 · NEI · WAYNE STATE UNIVERSITY · PI HAZLETT, LINDA D · 1985 to 2013
$6.2M
Role of Toll-Like Receptors in Bacterial KeratitisR01EY016058 · NEI · WAYNE STATE UNIVERSITY · PI HAZLETT, LINDA D · 2005 to 2023
$6.0M
NEI NIH HHS P30 EY004068NEI NIH HHS P30EY004068NEI NIH HHS R01 EY002986NEI NIH HHS R01EY002986NEI NIH HHS R01 EY016058NEI NIH HHS R01EY016058
6 · The paper itself

Abstract

High-mobility group box 1 (HMGB1), a prototypic alarmin, mediates the systemic inflammatory response syndrome. Treatment with vasoactive intestinal peptide, an anti-inflammatory neuropeptide, downregulates proinflammatory cytokines and promotes healing in a susceptible (cornea perforates) model of Pseudomonas aeruginosa keratitis, and also significantly downregulates HMGB1 expression. Therefore, we examined targeting HMGB1 for the treatment of P. aeruginosa keratitis to avoid delivery and other issues associated with vasoactive intestinal peptide. For this, HMGB1 was silenced using small interfering RNA, whereas controls were treated with a nonspecific scrambled sequence small interfering RNA. Less disease was seen postinfection in siHMGB1 compared with control mice and was documented by clinical score and photographs with a slit lamp. Real-time RT-PCR and ELISA confirmed HMGB1 knockdown. RT-PCR analysis also revealed reduced mRNA levels of IL-1β, MIP-2, TNF-α, TLR4, and receptor for advanced glycation end products, whereas mRNA levels of anti-inflammatory TLRs single Ig IL-1-related receptor and ST2 were increased significantly. HMGB1 knockdown also decreased IL-1β and MIP-2 proteins, reducing polymorphonuclear cell number in the infected cornea. mRNA and protein levels of CXCL12 and CXCR4, as well as mononuclear cells, were reduced significantly after HMGB1 knockdown. Ab neutralization of HMGB1, infection with a clinical isolate, and recombinant HMGB1 treatment of resistant mice supported the silencing studies. These data provide evidence that silencing HMGB1 promotes better resolution of P. aeruginosa keratitis by decreasing levels of proinflammatory mediators (decreasing polymorphonuclear cell infiltration), increasing anti-inflammatory TLRs, reducing CXCL12 (preventing HMGB1/CXCL12 heterodimer formation), and signaling through CXCR4, reducing monocyte/macrophage infiltration.

Indexed as

AnimalsDisease Models, AnimalEnzyme-Linked Immunosorbent AssayEye Infections, BacterialFemaleGene Knockdown TechniquesHMGB1 ProteinImmunohistochemistryKeratitisMiceMice, Inbred BALB CMice, Inbred C57BLPseudomonas aeruginosaPseudomonas InfectionsReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionHMGB1 ProteinHMGB1 protein, mouseRNA, Small Interfering

Identifiers

PMID25589066
PMCPMC4323849
OpenAlexW1586162470

What OpenQuestion holds

Textmetadata
LicenceTDM
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.