The Lipid Receptor G2A (GPR132) Mediates Macrophage Migration in Nerve Injury-Induced Neuropathic Pain

Osthues, Tabea; Zimmer, Béla; Rimola, Vittoria; Klann, Kevin; Schilling, Karin; Mathoor, Praveen; Angioni, Carlo; Weigert, Andreas; Geißlinger, Gerd; Münch, Christian; Scholich, Klaus; Sisignano, Marco

doi:10.3390/cells9071740

Cited by 21 publications

(11 citation statements)

References 81 publications

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“…Moreover, TDAG8 seems to contribute to cancer-induced pain via PKA activation in spinal microglia [78]. In contrast, G2A seems to contribute to oxaliplatininduced mechanical hypersensitivity via interaction with the TRPV1 channel in sensory neurons and mediates macrophage migration by activation of the Toll-like receptor 4 (TLR4) pathway in early nerve-injury-induced neuropathic pain [109,135].…”

Section: Proton-sensing Gpcrs In Persistent Pain Statesmentioning

confidence: 99%

Proton-Sensing GPCRs in Health and Disease

Sisignano

Fischer

Geißlinger

2021

Cells

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The group of proton-sensing G-protein coupled receptors (GPCRs) consists of the four receptors GPR4, TDAG8 (GPR65), OGR1 (GPR68), and G2A (GPR132). These receptors are cellular sensors of acidification, a property that has been attributed to the presence of crucial histidine residues. However, the pH detection varies considerably among the group of proton-sensing GPCRs and ranges from pH of 5.5 to 7.8. While the proton-sensing GPCRs were initially considered to detect acidic cellular environments in the context of inflammation, recent observations have expanded our knowledge about their physiological and pathophysiological functions and many additional individual and unique features have been discovered that suggest a more differentiated role of these receptors in health and disease. It is known that all four receptors contribute to different aspects of tumor biology, cardiovascular physiology, and asthma. However, apart from their overlapping functions, they seem to have individual properties, and recent publications identify potential roles of individual GPCRs in mechanosensation, intestinal inflammation, oncoimmunological interactions, hematopoiesis, as well as inflammatory and neuropathic pain. Here, we put together the knowledge about the biological functions and structural features of the four proton-sensing GPCRs and discuss the biological role of each of the four receptors individually. We explore all currently known pharmacological modulators of the four receptors and highlight potential use. Finally, we point out knowledge gaps in the biological and pharmacological context of proton-sensing GPCRs that should be addressed by future studies.

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Section: Proton-sensing Gpcrs In Persistent Pain Statesmentioning

confidence: 99%

Proton-Sensing GPCRs in Health and Disease

Sisignano

Fischer

Geißlinger

2021

Cells

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“…Two short-chain fatty acid receptors were also elevated, FFAR2 (or GPR43) and GPR132. GPR132 is a receptor expressed in tumor-associated macrophages [57][58][59], and the engagement of GPR132 attenuates inflammatory cytokines [60]. In addition, GPR132 senses lactate in the environment, which may favor the presence of beneficial lactateproducing bacteria.…”

Section: Discussionmentioning

confidence: 99%

LACTOCOCCUS LACTIS DELIVERY OF SURFACE LAYER PROTEIN A PROTECTS MICE FROM COLITIS BY RE-SETTING HOST IMMUNE REPERTOIRE

Sahay¹

2022

Inflammatory Bowel Diseases

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Inflammatory bowel disease (IBD) is characterized by gastrointestinal inflammation comprised of Crohn’s disease and ulcerative colitis. Centers for Disease Control and Prevention report that 1.3% of the population of the United States (approximately 3 million people) were affected by the disease in 2015, and the number keeps increasing over time. IBD has a multifactorial etiology, from genetic to environmental factors. Most of the IBD treatments revolve around disease management, by reducing the inflammatory signals. We previously identified the surface layer protein A (SlpA) of Lactobacillus acidophilus that possesses anti-inflammatory properties to mitigate murine colitis. Herein, we expressed SlpA in a clinically relevant, food-grade Lactococcus lactis to further investigate and characterize the protective mechanisms of the actions of SlpA[1] . Oral administration of SlpA-expressing L. lactis (R110) mitigated the symptoms of murine colitis. Oral delivery of R110 resulted in a higher expression of IL-27 by myeloid cells, with a synchronous increase in IL-10 and cMAF in T cells. Consistent with murine studies, human dendritic cells exposed to R110 showed exquisite differential gene regulation, including IL-27 transcription, suggesting a shared mechanism between the two species, hence positioning R110 as potentially effective at treating colitis in humans.

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“…Two short-chain fatty acid receptors were also elevated, FFAR2 (or GPR43) and GPR132. GPR132 is a receptor expressed in tumor-associated macrophages [ 57 , 58 , 59 ], and the engagement of GPR132 attenuates inflammatory cytokines [ 60 ]. In addition, GPR132 senses lactate in the environment, which may favor the presence of beneficial lactate-producing bacteria.…”

Section: Discussionmentioning

confidence: 99%

Lactococcus lactis Delivery of Surface Layer Protein A Protects Mice from Colitis by Re-Setting Host Immune Repertoire

Arukha

Freguia²,

Mishra

et al. 2021

Biomedicines

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Inflammatory bowel disease (IBD) is characterized by gastrointestinal inflammation comprised of Crohn’s disease and ulcerative colitis. Centers for Disease Control and Prevention report that 1.3% of the population of the United States (approximately 3 million people) were affected by the disease in 2015, and the number keeps increasing over time. IBD has a multifactorial etiology, from genetic to environmental factors. Most of the IBD treatments revolve around disease management, by reducing the inflammatory signals. We previously identified the surface layer protein A (SlpA) of Lactobacillus acidophilus that possesses anti-inflammatory properties to mitigate murine colitis. Herein, we expressed SlpA in a clinically relevant, food-grade Lactococcus lactis to further investigate and characterize the protective mechanisms of the actions of SlpA. Oral administration of SlpA-expressing L. lactis (R110) mitigated the symptoms of murine colitis. Oral delivery of R110 resulted in a higher expression of IL-27 by myeloid cells, with a synchronous increase in IL-10 and cMAF in T cells. Consistent with murine studies, human dendritic cells exposed to R110 showed exquisite differential gene regulation, including IL-27 transcription, suggesting a shared mechanism between the two species, hence positioning R110 as potentially effective at treating colitis in humans.

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The Lipid Receptor G2A (GPR132) Mediates Macrophage Migration in Nerve Injury-Induced Neuropathic Pain

Cited by 21 publications

References 81 publications

Proton-Sensing GPCRs in Health and Disease

Proton-Sensing GPCRs in Health and Disease

LACTOCOCCUS LACTIS DELIVERY OF SURFACE LAYER PROTEIN A PROTECTS MICE FROM COLITIS BY RE-SETTING HOST IMMUNE REPERTOIRE

Lactococcus lactis Delivery of Surface Layer Protein A Protects Mice from Colitis by Re-Setting Host Immune Repertoire

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