Immune-metabolic receptor GPR84 surrogate and endogenous agonists, 6-OAU and lauric acid, alter Brucella abortus 544 infection in both in vitro and in vivo systems

Reyes, Alisha Wehdnesday Bernardo; Kim, Heejin; Huy, Nguyen Tien; Vu, Son Hai; Nguyen, Trang Thi; Kang, Chang Keun; Min, Wongi; Lee, Hu Jang; Lee, John Hwa; Kim, Suk

doi:10.1016/j.micpath.2021.105079

Cited by 8 publications

(6 citation statements)

References 45 publications

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“…In just two cases to date, opposite effects were observed. First, a decrease in CCL2 secretion with 6‐OAU treatment was observed by Reyes et al (2021) in RAW264.7 macrophages infected with Brucella abortus . Second, a decrease in Tnf expression was observed by Ohue‐Kitano et al (2023) with 6‐OAU treatment of palmitate‐stimulated RAW264.7 cells.…”

Section: Effects Of Gpr84 Agonists On Innate Immune Cellsmentioning

confidence: 81%

Biased agonists of GPR84 and insights into biological control

Luscombe,

Wang,

Russell

et al. 2024

British J Pharmacology

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GPR84 was first identified as an open reading frame encoding an orphan Class A G protein coupled receptor in 2001. Gpr84 mRNA is expressed in a limited number of cell types with the highest levels of expression being in innate immune cells, M1 polarised macrophages and neutrophils. The first reported ligands for this receptor were medium chain fatty acids with chain lengths between 9 and 12 carbons. Subsequently a series of synthetic agonists that signal via the GPR84 receptor were identified. Radioligand binding assays and molecular modelling with site‐directed mutagenesis suggest the presence of three ligand binding sites on the receptor, but the physiological agonist(s) of the receptor remain unidentified. Here, we review the effects of GPR84 agonists on innate immune cells following a series of chemical discoveries since 2001. The development of highly biased agonists has helped to probe receptor function in vitro, and the remaining challenge is to follow the effects of biased signalling to the physiological functions of innate immune cell types.

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Section: Effects Of Gpr84 Agonists On Innate Immune Cellsmentioning

confidence: 81%

Biased agonists of GPR84 and insights into biological control

Luscombe,

Wang,

Russell

et al. 2024

British J Pharmacology

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“…The plate was centrifuged in a sealed carrier at 200 × g for 5 min and further incubated at indicated times. For adhesion assay, infected cells were washed at 0.5 h post-infection time to remove unassociated bacteria as previously described [ 20 ]. The cells were then lysed using 100 μl distilled water, pipette mixed, and 10 μl was diluted in PBS.…”

Section: Methodsmentioning

confidence: 99%

Protective Effects against Brucella abortus 544 Infection in a Murine Macrophage Cell Line and in a Mouse Model via Treatment with Sirtuin 1 Activators Resveratrol, Piceatannol and Ginsenoside Rg3

Reyes

Kim

Huy

et al. 2023

J. Microbiol. Biotechnol.

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Brucellosis is a contagious zoonotic disease that infects millions of people annually with hundreds of millions more being exposed. It is caused by Brucella , a highly infectious bacterial species capable of infecting humans with an estimated dose of 10-100 organisms. Sirtuin 1 (SIRT1) has been reported to contribute to prevention of viral diseases as well as a chronic infection caused by Mycobacterium bovis . Here, we investigated the role of SIRT1 in the establishment of Brucella abortus infection in both in vitro and in vivo systems using the reported SIRT1 activators resveratrol (RES), piceatannol (PIC), and ginsenoside Rg3 (Rg3). In RAW264.7 cells, SIRT1 activators did not alter the adherence of Brucella or Salmonella Typhimurium. However, reduced uptake of Brucella was observed in cells treated with PIC and Rg3, and survival of Brucella within the cells was only observed to decrease in cells that were treated with Rg3, while PIC treatment reduced the intracellular survival of Salmonella . SIRT1 treatment in mice via oral route resulted in augmented Brucella resistance for PIC and Rg3, but not RES. PIC treatment favors Th2 immune response despite reduced serum proinflammatory cytokine production, while Rg3-treated mice displayed high IL-12 and IFN-γ serum production. Overall, our findings encourage further investigation into the complete mechanisms of action of the different SIRT1 activators used as well as their potential benefit as an effective alternative approach against intracellular and extracellular pathogens.

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“…Additionally, GPR84 is also associated with the inflammatory response caused by bacterial pathogens such as Brucella abortus , responsible for human zoonosis (animal to human) disease. This protective role is attributed to the activation of GPR84 by both its synthetic (6‐OAU) and natural (lauric acid) agonist, where 6‐OAU and lauric acid inhibit adhesion and uptake of Brucella and reduce secretion of CCL2 in the murine macrophage cell line RAW264.7 (Reyes et al, 2021).…”

Section: Gpr84: Involvment In Pathophysiologymentioning

confidence: 99%

GPR84 in physiology—Many functions in many tissues

Aktar

Rondinelli

Peiris

2023

British J Pharmacology

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Members of the GPCR superfamily have a wide variety of physiological roles and are therefore valuable targets for developing effective medicines. However, within this superfamily are receptors that are less well characterised and remain orphans, including GPR84. This receptor, is stimulated by ligands derived from dietary nutrients, specifically medium chain fatty acids (MCFAs), and novel synthetic agonists. There is data demonstrating the role of GPR84 in inflammatory pathways, in addition to emerging data suggesting a key role for GPR84 as a nutrient‐sensing GPCR involved in metabolism by sensing energy load via nutrient exposure and subsequent signalling leading to modulation of food intake. Exploring GPR84 pharmacology, its localisation and what drives its expression reveals multiple roles for this receptor. Here, we will reflect on these various roles of GRP84 demonstrated thus far, primarily by exploring data from pre‐clinical and clinical studies in various physiological systems, with a specific focus on the gastrointestinal tract.

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Immune-metabolic receptor GPR84 surrogate and endogenous agonists, 6-OAU and lauric acid, alter Brucella abortus 544 infection in both in vitro and in vivo systems

Cited by 8 publications

References 45 publications

Biased agonists of GPR84 and insights into biological control

Biased agonists of GPR84 and insights into biological control

Protective Effects against Brucella abortus 544 Infection in a Murine Macrophage Cell Line and in a Mouse Model via Treatment with Sirtuin 1 Activators Resveratrol, Piceatannol and Ginsenoside Rg3

GPR84 in physiology—Many functions in many tissues

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