Uncovering the Power of GPR18 Signalling: How RvD2 and Other Ligands Could Have the Potential to Modulate and Resolve Inflammation in Various Health Disorders

Honkisz-Orzechowska, Ewelina; Łażewska, Dorota; Baran, Grzegorz; Kieć-Kononowicz, Katarzyna

doi:10.3390/molecules29061258

Cited by 3 publications

(1 citation statement)

References 89 publications

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“…M2 macrophages are hypothesized to expedite the progression of cardiac and tissue repair mechanisms [16,31]. In contrast, we observed a parallel decrease in pro-inflammatory M1-polarizing cytokines IL1, TNFα, INFγ, and GPR18 [29,32] in the heart and diaphragm muscle. The definitive polarization of macrophages occurs upon their localization at the fibrotic site, notably observed in organs such as the heart and diaphragm muscles [33].…”

Section: Discussionmentioning

confidence: 57%

Cardioprotection and Suppression of Fibrosis by Diverse Cancer and Non-Cancer Cell Lines in a Murine Model of Duchenne Muscular Dystrophy

Achlaug,

Langier Goncalves,

Aronheim

2024

IJMS

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The dynamic relationship between heart failure and cancer poses a dual challenge. While cardiac remodeling can promote cancer growth and metastasis, tumor development can ameliorate cardiac dysfunction and suppress fibrosis. However, the precise mechanism through which cancer influences the heart and fibrosis is yet to be uncovered. To further explore the interaction between heart failure and cancer, we used the MDX mouse model, which suffers from cardiac fibrosis and cardiac dysfunction. A previous study from our lab demonstrated that tumor growth improves cardiac dysfunction and dampens fibrosis in the heart and diaphragm muscles of MDX mice. We used breast Polyoma middle T (PyMT) and Lewis lung carcinoma (LLC) cancer cell lines that developed into large tumors. To explore whether the aggressiveness of the cancer cell line is crucial for the beneficial phenotype, we employed a PyMT breast cancer cell line lacking integrin β1, representing a less aggressive cell line compared to the original PyMT cells. In addition, we examined immortalized and primary MEF cells. The injection of integrin β1 KO PyMT cancer cells and Mouse Embryo Fibroblasts cells (MEF) resulted in the improvement of cardiac function and decreased fibrosis in the heart, diaphragm, and skeletal muscles of MDX mice. Collectively, our data demonstrate that the cancer line aggressiveness as well as primary MEF cells are sufficient to impose the beneficial phenotype. These discoveries present potential novel clinical therapeutic approaches with beneficial outcome for patients with fibrotic diseases and cardiac dysfunction that do not require tumor growth.

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Section: Discussionmentioning

confidence: 57%

Cardioprotection and Suppression of Fibrosis by Diverse Cancer and Non-Cancer Cell Lines in a Murine Model of Duchenne Muscular Dystrophy

Achlaug,

Langier Goncalves,

Aronheim

2024

IJMS

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Naringin dihydrochalcone alleviates sepsis-induced acute lung injury via improving gut microbial homeostasis and activating GPR18 receptor

He,

Zhuo,

Cui

et al. 2024

International Immunopharmacology

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

Wang,

Banga,

Ebrahim

et al. 2024

Front. Immunol.

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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.

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Uncovering the Power of GPR18 Signalling: How RvD2 and Other Ligands Could Have the Potential to Modulate and Resolve Inflammation in Various Health Disorders

Cited by 3 publications

References 89 publications

Cardioprotection and Suppression of Fibrosis by Diverse Cancer and Non-Cancer Cell Lines in a Murine Model of Duchenne Muscular Dystrophy

Cardioprotection and Suppression of Fibrosis by Diverse Cancer and Non-Cancer Cell Lines in a Murine Model of Duchenne Muscular Dystrophy

Naringin dihydrochalcone alleviates sepsis-induced acute lung injury via improving gut microbial homeostasis and activating GPR18 receptor

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

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