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Article ; Online: Inflammation and Infection in Pain and the Role of GPR37.

Zhang, Qin / Bang, Sangsu / Chandra, Sharat / Ji, Ru-Rong

International journal of molecular sciences

2022 Volume 23, Issue 22

Abstract: Inflammation is known to cause pain, and pain is of one of the cardinal signs of inflammation. Mounting evidence suggests that acute inflammation also resolves pain through specialized pro-resolving mediators (SPMs) and macrophage signaling. GPR37 is ... ...

Abstract	Inflammation is known to cause pain, and pain is of one of the cardinal signs of inflammation. Mounting evidence suggests that acute inflammation also resolves pain through specialized pro-resolving mediators (SPMs) and macrophage signaling. GPR37 is expressed by neurons and oligodendrocytes in the brain and has been implicated in multiple disorders, such as demyelination, Parkinson's disease, stroke, and cancer. Recent studies have demonstrated that GPR37 is expressed by macrophages and confers protection against infection by bacteria and parasites. Furthermore, GPR37 promotes the resolution of inflammatory pain and infection-induced pain, as the duration of pain after tissue injury and infection is prolonged in mice lacking
MeSH term(s)	Animals ; Mice ; Inflammation/prevention & control ; Phagocytosis ; Macrophages ; Anti-Inflammatory Agents/pharmacology ; Neuralgia ; Receptors, G-Protein-Coupled
Chemical Substances	Anti-Inflammatory Agents ; Gpr37 protein, mouse ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2022-11-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232214426
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Article ; Online: SHANK3 in vagal sensory neurons regulates body temperature, systemic inflammation, and sepsis.

Zhang, Linlin / Bang, Sangsu / He, Qianru / Matsuda, Megumi / Luo, Xin / Jiang, Yong-Hui / Ji, Ru-Rong

Frontiers in immunology

2023 Volume 14, Page(s) 1124356

Abstract: Excessive inflammation has been implicated in autism spectrum disorder (ASD), but the underlying mechanisms have not been fully studied. SHANK3 is a synaptic scaffolding protein and mutations ... ...

Abstract	Excessive inflammation has been implicated in autism spectrum disorder (ASD), but the underlying mechanisms have not been fully studied. SHANK3 is a synaptic scaffolding protein and mutations of
MeSH term(s)	Mice ; Animals ; Autism Spectrum Disorder ; Body Temperature ; Lipopolysaccharides ; TRPM Cation Channels ; Interleukin-6 ; Sensory Receptor Cells ; Sepsis ; Inflammation ; Microfilament Proteins ; Nerve Tissue Proteins/genetics
Chemical Substances	Lipopolysaccharides ; TRPM Cation Channels ; Interleukin-6 ; Shank3 protein, mouse ; Microfilament Proteins ; Nerve Tissue Proteins ; TRPM2 protein, mouse
Language	English
Publishing date	2023-02-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1124356
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Article ; Online: Satellite glial GPR37L1 and its ligand maresin 1 regulate potassium channel signaling and pain homeostasis.

Bang, Sangsu / Jiang, Changyu / Xu, Jing / Chandra, Sharat / McGinnis, Aidan / Luo, Xin / He, Qianru / Li, Yize / Wang, Zilong / Ao, Xiang / Parisien, Marc / Oliveira Fernandes de Araujo, Lorenna / Jahangiri Esfahani, Sahel / Zhang, Qin / Tonello, Raquel / Berta, Temugin / Diatchenko, Luda / Ji, Ru-Rong

The Journal of clinical investigation

2024

Abstract: G protein-coupled receptor 37-like 1 (GPR37L1) is an orphan GPCR with largely unknown functions. Here we report that Gpr37l1/GRP37L1 ranks among the most highly expressed GPCR transcripts in mouse and human dorsal root ganglia (DRGs), selectively ... ...

Abstract	G protein-coupled receptor 37-like 1 (GPR37L1) is an orphan GPCR with largely unknown functions. Here we report that Gpr37l1/GRP37L1 ranks among the most highly expressed GPCR transcripts in mouse and human dorsal root ganglia (DRGs), selectively expressed in satellite glial cells (SGCs). Peripheral neuropathy induced by streptozotoxin (STZ) and paclitaxel (PTX) led to reduced GPR37L1 expression on the plasma membrane expression in mouse and human DRGs. Transgenic mice with Gpr37l1 deficiency exhibited impaired resolution of neuropathic pain symptoms following PTX and STZ-induced pain, whereas overexpression of Gpr37l1 in mouse DRGs reversed pain. GPR37L1 is co-expressed with potassium channels, including KCNJ10 (Kir4.1) in mouse SGCs and both KCNJ3 (Kir3.1) and KCNJ10 in human SGCs. GPR37L1 regulates the surface expression and function of the potassium channels. Notably, the pro-resolving lipid mediator maresin 1 (MaR1) serves as a ligand of GPR37L1 and enhances KCNJ10 or KCNJ3-mediated potassium influx in SGCs through GPR37L1. Chemotherapy suppressed KCNJ10 expression and function in SGCs, which MaR1 rescued through GPR37L1. Finally, genetic analysis revealed that the GPR37L1-E296K variant increased chronic pain risk by destabilizing the protein and impairing the protein's function. Thus, GPR37L1 in SGCs offers a new therapeutic target for the protection of neuropathy and chronic pain.
Language	English
Publishing date	2024-03-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI173537
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Ua VI Zs.184: Show issues

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bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: PD-L1/PD-1 checkpoint pathway regulates hippocampal neuronal excitability and learning and memory behavior.

Zhao, Junli / Bang, Sangsu / Furutani, Kenta / McGinnis, Aidan / Jiang, Changyu / Roberts, Alexus / Donnelly, Christopher R / He, Qianru / James, Michael L / Berger, Miles / Ko, Mei-Chuan / Wang, Haichen / Palmiter, Richard D / Ji, Ru-Rong

Neuron

2023 Volume 111, Issue 17, Page(s) 2709–2726.e9

Abstract: Programmed death protein 1 (PD-1) and its ligand PD-L1 constitute an immune checkpoint pathway. We report that neuronal PD-1 signaling regulates learning/memory in health and disease. Mice lacking PD-1 (encoded by Pdcd1) exhibit enhanced long-term ... ...

Abstract	Programmed death protein 1 (PD-1) and its ligand PD-L1 constitute an immune checkpoint pathway. We report that neuronal PD-1 signaling regulates learning/memory in health and disease. Mice lacking PD-1 (encoded by Pdcd1) exhibit enhanced long-term potentiation (LTP) and memory. Intraventricular administration of anti-mouse PD-1 monoclonal antibody (RMP1-14) potentiated learning and memory. Selective deletion of PD-1 in excitatory neurons (but not microglia) also enhances LTP and memory. Traumatic brain injury (TBI) impairs learning and memory, which is rescued by Pdcd1 deletion or intraventricular PD-1 blockade. Conversely, re-expression of Pdcd1 in PD-1-deficient hippocampal neurons suppresses memory and LTP. Exogenous PD-L1 suppresses learning/memory in mice and the excitability of mouse and NHP hippocampal neurons through PD-1. Notably, neuronal activation suppresses PD-L1 secretion, and PD-L1/PD-1 signaling is distinctly regulated by learning and TBI. Thus, conditions that reduce PD-L1 levels or PD-1 signaling could promote memory in both physiological and pathological conditions.
MeSH term(s)	Humans ; B7-H1 Antigen/metabolism ; Programmed Cell Death 1 Receptor/genetics ; Programmed Cell Death 1 Receptor/metabolism ; Learning ; Hippocampus/metabolism ; Antibodies, Monoclonal/metabolism ; Brain Injuries, Traumatic ; Neurons/metabolism
Chemical Substances	B7-H1 Antigen ; Programmed Cell Death 1 Receptor ; Antibodies, Monoclonal
Language	English
Publishing date	2023-06-21
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2023.05.022
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Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 92: Show issues

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Article ; Online: Intrathecal administration of conditioned serum from different species resolves Chemotherapy-Induced neuropathic pain in mice via secretory exosomes.

Buchheit, Thomas / Huh, Yul / Breglio, Andrew / Bang, Sangsu / Xu, Jing / Matsuoka, Yutaka / Guo, Ran / Bortsov, Andrey / Reinecke, Julio / Wehling, Peter / Jun Huang, Tony / Ji, Ru-Rong

Brain, behavior, and immunity

2023 Volume 111, Page(s) 298–311

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication of chemotherapy for cancer, and has limited effective treatment options. Autologous conditioned serum (ACS) is an effective biologic therapy used by intra- ... ...

Abstract	Chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication of chemotherapy for cancer, and has limited effective treatment options. Autologous conditioned serum (ACS) is an effective biologic therapy used by intra-articular injection for patients with osteoarthritis. However, ACS has not been systematically tested in the treatment of peripheral neuropathies such as CIPN. It has been generally assumed that the analgesic effect of this biologic therapy results from augmented concentrations of anti-inflammatory cytokines and growth factors. Here we report that a single intrathecal injection of human conditioned serum (hCS) produced long-lasting inhibition of paclitaxel chemotherapy-induced neuropathic pain (mechanical allodynia) in mice, without causing motor impairment. Strikingly, the analgesic effect of hCS in our experiments was maintained even 8 weeks after the treatment, compared with non-conditioned human serum (hNCS). Furthermore, the hCS transfer-induced pain relief in mice was fully recapitulated by rat or mouse CS transfer to mice of both sexes, indicating cross-species and cross-sex effectiveness. Mechanistically, CS treatment blocked the chemotherapy-induced glial reaction in the spinal cord and improved nerve conduction. Compared to NCS, CS contained significantly higher concentrations of anti-inflammatory and pro-resolving mediators, including IL-1Ra, TIMP-1, TGF-β1, and resolvins D1/D2. Intrathecal injection of anti-TGF-β1 and anti-Il-1Ra antibody transiently reversed the analgesic action of CS. Nanoparticle tracking analysis revealed that rat conditioned serum contained a significantly greater number of exosomes than NCS. Importantly, the removal of exosomes by high-speed centrifugation largely diminished the CS-produced pain relief, suggesting a critical involvement of small vesicles (exosomes) in the beneficial effects of CS. Together, our findings demonstrate that intrathecal CS produces a remarkable resolution of neuropathic pain mediated through a combination of small vesicles/exosomes and neuroimmune/neuroglial modulation.
MeSH term(s)	Male ; Female ; Mice ; Rats ; Humans ; Animals ; Exosomes/metabolism ; Neuralgia/metabolism ; Paclitaxel/adverse effects ; Hyperalgesia/metabolism ; Spinal Cord/metabolism ; Analgesics/pharmacology ; Antineoplastic Agents/adverse effects
Chemical Substances	Paclitaxel (P88XT4IS4D) ; Analgesics ; Antineoplastic Agents
Language	English
Publishing date	2023-05-05
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2023.04.013
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Zs.A 2276: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 327: Show issues

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Article: Satellite glial GPR37L1 regulates maresin and potassium channel signaling for pain control.

Bang, Sangsu / Jiang, Changyu / Xu, Jing / Chandra, Sharat / McGinnis, Aidan / Luo, Xin / He, Qianru / Li, Yize / Wang, Zilong / Ao, Xiang / Parisien, Marc / Fernandes de Araujo, Lorenna Oliveira / Esfahan, Sahel Jahangiri / Zhang, Qin / Tonello, Raquel / Berta, Temugin / Diatchenko, Luda / Ji, Ru-Rong

bioRxiv : the preprint server for biology

2023

Abstract: G protein coupled receptor 37-like 1 (GPR37L1) is an orphan GPCR and its function remains largely unknown. Here we report that GPR37L1 transcript is highly expressed compared to all known GPCRs in mouse and human dorsal root ganglia (DRGs) and ... ...

Abstract	G protein coupled receptor 37-like 1 (GPR37L1) is an orphan GPCR and its function remains largely unknown. Here we report that GPR37L1 transcript is highly expressed compared to all known GPCRs in mouse and human dorsal root ganglia (DRGs) and selectively expressed in satellite glial cells (SGCs). Peripheral neuropathy following diabetes and chemotherapy by streptozotocin and paclitaxel resulted in downregulations of surface GPR37L1 in mouse and human DRGs. Transgenic mice with
Language	English
Publishing date	2023-12-05
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.03.569787
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Article ; Online: IL-23 Enhances C-Fiber-Mediated and Blue Light-Induced Spontaneous Pain in Female Mice.

Ji, Jasmine / He, Qianru / Luo, Xin / Bang, Sangsu / Matsuoka, Yutaka / McGinnis, Aidan / Nackley, Andrea G / Ji, Ru-Rong

Frontiers in immunology

2021 Volume 12, Page(s) 787565

Abstract: The incidence of chronic pain is especially high in women, but the underlying mechanisms remain poorly understood. Interleukin-23 (IL-23) is a pro-inflammatory cytokine and contributes to inflammatory diseases (e.g., arthritis and psoriasis) through ... ...

Abstract	The incidence of chronic pain is especially high in women, but the underlying mechanisms remain poorly understood. Interleukin-23 (IL-23) is a pro-inflammatory cytokine and contributes to inflammatory diseases (e.g., arthritis and psoriasis) through dendritic/T cell signaling. Here we examined the IL-23 involvement in sexual dimorphism of pain, using an optogenetic approach in transgenic mice expressing channelrhodopsin-2 (ChR2) in TRPV1-positive nociceptive neurons.
MeSH term(s)	Animals ; Capsaicin ; Channelrhodopsins/genetics ; Channelrhodopsins/metabolism ; Disease Models, Animal ; Female ; Ganglia, Spinal/drug effects ; Ganglia, Spinal/metabolism ; Ganglia, Spinal/physiopathology ; Humans ; Interleukin-17/metabolism ; Interleukin-23/toxicity ; Light ; Macrophages/drug effects ; Macrophages/metabolism ; Male ; Mice, Inbred C57BL ; Mice, Transgenic ; Nerve Fibers, Unmyelinated/drug effects ; Nerve Fibers, Unmyelinated/metabolism ; Nociceptors/drug effects ; Nociceptors/metabolism ; Optogenetics ; Pain/chemically induced ; Pain/genetics ; Pain/metabolism ; Pain/physiopathology ; Pain Threshold/drug effects ; Sex Characteristics ; THP-1 Cells ; TRPV Cation Channels/genetics ; TRPV Cation Channels/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism ; Mice
Chemical Substances	Channelrhodopsins ; IL17A protein, human ; Interleukin-17 ; Interleukin-23 ; TRPV Cation Channels ; TRPV1 protein, mouse ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Capsaicin (S07O44R1ZM)
Language	English
Publishing date	2021-12-07
Publishing country	Switzerland
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.787565
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Article ; Online: Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice

Sangsu Bang / Christopher R. Donnelly / Xin Luo / Maria Toro-Moreno / Xueshu Tao / Zilong Wang / Sharat Chandra / Andrey V. Bortsov / Emily R. Derbyshire / Ru-Rong Ji

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 17

Abstract: GPR37 is expressed in macrophages, and has been implicated in resolution of inflammatory pain. Here the authors show that GPR37 can modulate sepsis in several animal models. ...

Abstract	GPR37 is expressed in macrophages, and has been implicated in resolution of inflammatory pain. Here the authors show that GPR37 can modulate sepsis in several animal models.
Keywords	Science ; Q
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: STING suppresses bone cancer pain via immune and neuronal modulation

Kaiyuan Wang / Christopher R. Donnelly / Changyu Jiang / Yihan Liao / Xin Luo / Xueshu Tao / Sangsu Bang / Aidan McGinnis / Michael Lee / Matthew J. Hilton / Ru-Rong Ji

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 21

Abstract: There is an unmet clinical need to develop therapies to alleviate metastatic bone pain, frequently observed in patients with advanced cancers. Here, using mouse models of bone cancer pain, the authors show that STING agonists not only suppress bone ... ...

Abstract	There is an unmet clinical need to develop therapies to alleviate metastatic bone pain, frequently observed in patients with advanced cancers. Here, using mouse models of bone cancer pain, the authors show that STING agonists not only suppress bone cancer tumor burden, but also attenuate bone pain and reduce cancer-induced bone destruction.
Keywords	Science ; Q
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice.

Bang, Sangsu / Donnelly, Christopher R / Luo, Xin / Toro-Moreno, Maria / Tao, Xueshu / Wang, Zilong / Chandra, Sharat / Bortsov, Andrey V / Derbyshire, Emily R / Ji, Ru-Rong

Nature communications

2021 Volume 12, Issue 1, Page(s) 1704

Abstract: GPR37 was discovered more than two decades ago, but its biological functions remain poorly understood. Here we report a protective role of GPR37 in multiple models of infection and sepsis. Mice lacking Gpr37 exhibited increased death and/or hypothermia ... ...

Abstract	GPR37 was discovered more than two decades ago, but its biological functions remain poorly understood. Here we report a protective role of GPR37 in multiple models of infection and sepsis. Mice lacking Gpr37 exhibited increased death and/or hypothermia following challenge by lipopolysaccharide (LPS), Listeria bacteria, and the mouse malaria parasite Plasmodium berghei. Sepsis induced by LPS and Listeria in wild-type mice is protected by artesunate (ARU) and neuroprotectin D1 (NPD1), but the protective actions of these agents are lost in Gpr37
MeSH term(s)	Adoptive Transfer ; Animals ; Artesunate/metabolism ; Artesunate/pharmacology ; Artesunate/therapeutic use ; Disease Models, Animal ; Docosahexaenoic Acids/metabolism ; Docosahexaenoic Acids/pharmacology ; Docosahexaenoic Acids/therapeutic use ; Lipopolysaccharides/toxicity ; Listeria monocytogenes/pathogenicity ; Macrophages/drug effects ; Macrophages/metabolism ; Macrophages/pathology ; Macrophages/transplantation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular Docking Simulation ; Pain/immunology ; Pain/mortality ; Pain/prevention & control ; Phagocytosis/drug effects ; Plasmodium berghei/pathogenicity ; Receptors, G-Protein-Coupled/deficiency ; Receptors, G-Protein-Coupled/metabolism ; Sepsis/immunology ; Sepsis/mortality ; Sepsis/prevention & control ; Sepsis/therapy
Chemical Substances	Gpr37 protein, mouse ; Lipopolysaccharides ; Receptors, G-Protein-Coupled ; protectin D1 ; Docosahexaenoic Acids (25167-62-8) ; Artesunate (60W3249T9M)
Language	English
Publishing date	2021-03-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-21940-8
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