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Study · Animal study (in vivo) · 2024

4 results

Activation of pro-resolving pathways mediate the therapeutic effects of thymosin beta-4 during Pseudomonas aeruginosa-induced keratitis.

Wang Y, Banga L, Ebrahim AS, Carion TW, Sosne G, Berger EA

Frontiers in immunology24 Sept 2024

Summary

IntroductionCurrent treatments for bacterial keratitis fail to address the sight-threatening inflammatory host response. Our recent work elucidating the therapeutic mechanisms of adjunctive thymosin beta-4 (Tβ4) in resolving inflammation and infection in bacterial keratitis revealed modulation of effector cell function and enhanced bacterial killing. The current study builds upon the observed effects on effector cell function by investigating the impact of Tβ4 on specialized pro-resolving lipid mediator (SPM) pathways as they play a significant role in inflammation resolution.MethodsUsing a well-established in vivo model of Pseudomonas aeruginosa-induced bacterial keratitis, we assessed key enzymes (5-LOX and 12/15-LOX) involved in SPM pathway activation, SPM end products (lipoxins, resolvins), and receptor levels for these mediators. In vitro validation using LPS-stimulated murine monocyte/MΦ-like RAW 264.7 cells and siRNA to inhibit Tβ4 and LOX enzymes was carried out to complement our in vivo findings.ResultsFindings from our in vivo and in vitro investigations demonstrated that adjunctive Tβ4 treatment significantly influences enzymes and receptors involved in SPM pathways. Further, Tβ4 alone enhances the generation of SPM end products in the cornea. Our in vitro assessments confirmed that Tβ4-enhanced phagocytosis is directly mediated by SPM pathway activation. Whereas Tβ4-enhanced efferocytosis appeared to be indirect.ConclusionCollectively, these findings suggest that the therapeutic effect of Tβ4 resolves inflammation through the activation of SPM pathways, thereby enhancing host defense and tissue repair. Our research contributes to understanding the potential mechanisms behind Tβ4 immunoregulatory function, pointing to its promising ability as a comprehensive adjunctive treatment for bacterial keratitis.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Mechanism

    In Pseudomonas aeruginosa keratitis models, adjunctive Tβ4 significantly influenced enzymes and receptors of specialized pro-resolving mediator pathways.

    In plain wordsIn a bacterial eye infection model, Tβ4 changed enzymes and receptors involved in resolving inflammation.

    Outcome
    Direction not reportedSPM pathway enzymes and receptors
    Study

    n: not reported in source

    Pseudomonas aeruginosa keratitis model
    Outcome group
    Inflammation markers · Eye
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Findings from our in vivo and in vitro investigations demonstrated that adjunctive Tβ4 treatment significantly influences enzymes and receptors involved in SPM pathways.
    1 context sentence
    Summary · context
    Using a well-established in vivo model of Pseudomonas aeruginosa-induced bacterial keratitis, we assessed key enzymes (5-LOX and 12/15-LOX) involved in SPM pathway activation, SPM end products (lipoxins, resolvins), and receptor levels for these mediators.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In Pseudomonas aeruginosa keratitis, Tβ4 alone enhanced the generation of SPM end products in the cornea.

    In plain wordsIn a bacterial eye infection model, Tβ4 alone increased the cornea's production of inflammation-resolving lipids.

    Outcome
    IncreaseSPM end product generation in cornea
    Study

    n: not reported in source

    Pseudomonas aeruginosa keratitis model
    Outcome group
    Inflammation markers · Eye
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Further, Tβ4 alone enhances the generation of SPM end products in the cornea.
    1 context sentence
    Summary · context
    Using a well-established in vivo model of Pseudomonas aeruginosa-induced bacterial keratitis, we assessed key enzymes (5-LOX and 12/15-LOX) involved in SPM pathway activation, SPM end products (lipoxins, resolvins), and receptor levels for these mediators.
  3. 03LabIn vitro (cells)Mechanism

    In LPS-stimulated RAW 264.7 cells, Tβ4-enhanced phagocytosis was directly mediated by SPM pathway activation.

    In plain wordsIn mouse immune cells in the lab, Tβ4 increased phagocytosis through the SPM pathway.

    Outcome
    IncreasePhagocytosis via SPM pathway
    Study

    mousen: not reported in source

    LPS-stimulated RAW 264.7 murine monocyte/macrophage-like cells
    Outcome group
    Immune response · Eye
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Our in vitro assessments confirmed that Tβ4-enhanced phagocytosis is directly mediated by SPM pathway activation.
    1 context sentence
    Summary · context
    In vitro validation using LPS-stimulated murine monocyte/MΦ-like RAW 264.7 cells and siRNA to inhibit Tβ4 and LOX enzymes was carried out to complement our in vivo findings.
  4. 04LabIn vitro (cells)Mechanism

    In LPS-stimulated RAW 264.7 cells, Tβ4-enhanced efferocytosis appeared to be mediated indirectly by SPM pathways.

    In plain wordsIn mouse immune cells in the lab, Tβ4 increased efferocytosis, apparently not directly through the SPM pathway.

    Outcome
    IncreaseEfferocytosis via SPM pathway
    Study

    mousen: not reported in source

    LPS-stimulated RAW 264.7 murine monocyte/macrophage-like cells
    Outcome group
    Immune response · Eye
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Whereas Tβ4-enhanced efferocytosis appeared to be indirect.
    1 context sentence
    Summary · context
    In vitro validation using LPS-stimulated murine monocyte/MΦ-like RAW 264.7 cells and siRNA to inhibit Tβ4 and LOX enzymes was carried out to complement our in vivo findings.

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Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    13 Oct 2026, 01:52 UTC

    Study results updated

  2. Version 1

    12 Oct 2026, 18:17 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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