G protein-coupled receptor 39 plays an anti-inflammatory role by enhancing IL-10 production from macrophages under inflammatory conditions

Muneoka, Satoshi; Goto, Megumi; Kadoshima-Yamaoka, Kumiko; Kamei, Reiko; Terakawa, Maki; Tomimori, Yoshiaki

doi:10.1016/j.ejphar.2018.07.045

Cited by 23 publications

(20 citation statements)

References 28 publications

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“…[ 22 ] As shown in Figure S1B, Supporting Information, 1 H NMR spectrum confirmed the characterized resonances of DSPE at 0.85 and 1.23 ppm, PEG at 3.44 ppm, and CB[7] at 4.65, 5.45 and 5.70 ppm, indicating the successful preparation of DSPE‐PEG‐CB[7]. Peritoneal macrophages were subsequently extracted from thioglycollate‐treated mice, [ 23 ] and the purity of F4/80 + CD11b + cells reached 90% (Figure S2, Supporting Information). Subsequently, the macrophages were incubated with 10 µ m of DSPE‐PEG‐CB[7] for 1.5 h, which was less than its critical micelle concentration (CMC) of ≈40 uM (Figure S3, Supporting Information), to prepare CB[7]‐Macrophage, here also referred to as “supramolecular macrophage” ( Figure A).…”

Section: Resultsmentioning

confidence: 78%

Supramolecular Macrophage‐Liposome Marriage for Cell‐Hitchhiking Delivery and Immunotherapy of Acute Pneumonia and Melanoma

Cheng

Qian

et al. 2021

Adv Funct Materials

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As many diseases are related to inflammation, the inflammatory tropism of immune cells may bring cell‐hitchhikers directly to the disease tissues in a highly targeted manner. The current cell‐hitchhiking strategies rely on either cellular internalization or covalent surface conjugation, which often affects the physiological function of transporting cells. Herein, a cell‐friendly, host‐guest chemistry mediated macrophage‐liposome conjugate (M‐L) is developed for extremely stable cell‐hitchhiking drug delivery. M‐L is prepared via simple supramolecular “hand‐holding” and marriage between cucurbit[7]uril (CB[7]) and adamantane, respectively anchored on the surface of the macrophage and liposome, which demonstrates targeted accumulation in the inflamed lung and effective therapy of acute pneumonia in mice when loaded with quercetin. Upon loading toxic chemotherapeutic agents (such as doxorubicin and oxaliplatin), M‐L carries the payloads to the inflammatory cancer tissue and significantly enhances the chemoimmunotherapy of melanoma in mice. Fundamentally, this CB[7]‐based supramolecular M‐L conjugation strategy shows negligible effects on the migratory and invasive behaviors of macrophages. In vivo pathological analysis of the inflammatory tissues in mice after treatment with M‐L further suggests that macrophage and liposomes are delivered together hand in hand. This CB[7]‐based, supramolecular cell‐conjugation strategy potentially addresses the key challenges faced by the current cell‐based delivery systems.

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Section: Resultsmentioning

confidence: 78%

Supramolecular Macrophage‐Liposome Marriage for Cell‐Hitchhiking Delivery and Immunotherapy of Acute Pneumonia and Melanoma

Cheng

Qian

et al. 2021

Adv Funct Materials

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“…In the process of GPR39 regulating the activity of endothelial cells, Zn+ is involved in the regulation of some in ammation-related key molecules including heme oxygenase-1, selectin L and IL-10 [53]. GPR39 was upregulated in thioglycollate-induced peritoneal macrophages and exerted its anti-in ammatory effects by increasing the production of IL-10 [27]. It has been shown that treatment with TC-G 1008 abolished the increased expression of pro-in ammatory cytokines induced by ox-LDL in the prevention of atherosclerosis [26].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, activation of GPR39 has been demonstrated to promote wound healing, ameliorate symptoms of in ammatory bowel diseases, dampen epileptic seizure activity, reduce anxietylike behaviors and regulate insulin secretion and malignant progression of several cancers [17][18][19][20][21][22][23][24]. Recently, accumulating in vitro evidence demonstrated that GPR39 exhibits anti-in ammatory activity by reducing the expression of pro-in ammatory cytokines(IL-1β IL-6), enhancing anti-in ammatory cytokines production (IL-10), ameliorating oxidative stress and mitochondrial dysfunction [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Activation of GPR39 With TC-G 1008 Attenuates Neuroinflammation Via SIRT1/PGC-1α/Nrf2 Pathway Post Neonatal Hypoxic-ischemic Injury in Rats

Xie

Jiang

Doycheva

et al. 2021

Preprint

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Background: Hypoxic-ischemic encephalopathy (HIE) is a severe anoxic brain injury that leads to premature mortality or long-term disabilities in infants. Neuroinflammation is a vital contributor to the pathogenic cascade post HIE and a mediator to secondary neuronal death. As a plasma membrane G-protein coupled receptor, GPR39, exhibits anti-inflammatory activity in several diseases. This study aimed to explore the neuroprotective function of GPR39 through inhibition of inflammation post hypoxic-ischemic (HI) injury and to elaborate the contribution of sirtuin 1(SIRT1)/ peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)/ nuclear factor, erythroid 2 like 2(Nrf2) in G protein-coupled receptor 39 (GPR39)-mediated protection.Methods: A total of 206 10-day old Sprague Dawley rat pups were subjected to HIE or sham surgery. TC-G 1008 was administered intranasally at 1h, 25h, 49h, and 73h post HIE induction. SIRT1 inhibitor EX527, GPR39 CRISPR, and PGC-1α CRISPR were administered to elucidate the underlying mechanisms. Brain infarct area, short-term and long-term neurobehavioral tests, Nissl staining, western blot, and immunofluorescence staining were performed post HIE.Results: The expression of GPR39 and pathway-related proteins, SIRT1、PGC-1α and Nrf2 were increased in a time-dependent manner, peaking at 24 h or 48h post HIE. Intranasal administration of TC-G 1008 reduced the percent infarcted area and improved short-term and long-term neurological deficits. Moreover, TC-G 1008 treatment significantly increased the expression of SIRT1, PGC-1α, Nrf2, IL-6, IL-1β, and TNF-α. GPR39 CRISPR EX527 and PGC-1α CRISPR abolished GPR39’s neuroprotective effects post HIE.Conclusions:TC-G 1008 attenuated neuroinflammation in part via the SIRT1/PGC-1α/Nrf2 pathway in a neonatal rat model of HIE. TC-G 1008 may be a novel therapeutic target for treatment post neonatal HIE injury.

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“…9) Following various reports implicating the receptor in pathophysiology of diseases such as metabolic syndrome, depression, and colitis and in wound healing, 10) a selective GPR39 agonist TC-G 1008 has been identified 11) and used as a pharmacological tool to clarify the physiological roles of GPR39. [12][13][14] In our report regarding an anti-inflammatory role of GPR39, we found that oral administration of TC-G 1008 increased Il-10 mRNA in the liver in lipopolysaccharide (LPS)-induced murine model of sepsis. These data suggested that GPR39 agonists could be effective in liver-related diseases, such as hepatitis.…”

Section: Introductionmentioning

confidence: 93%

G Protein-Coupled Receptor 39 Agonist Improves Concanavalin A-Induced Hepatitis in Mice

Muneoka¹,

Goto²,

Nishimura³

et al. 2019

Biological & Pharmaceutical Bulletin

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The protective effects of G protein-coupled receptor 39 (GPR39) on concanavalin A (Con A)-induced hepatitis in mice was examined. In a dose dependent manner and at 24 h after the elicitation by Con A, oral administration of TC-G 1008, a GPR39 agonist, reduced both, the glutamic-pyruvic transaminase levels (a marker for liver injury) and the necrosis area, as revealed by the histological analysis of tissues from mice with Con A-induced hepatitis. TC-G 1008 also suppressed serum interleukin (IL)-6 and tumor necrosis factor (TNF)-α significantly at 6 h after the elicitation, suggesting that the cells producing IL-6 and/or TNF-α are the targets of TC-G 1008. One potential target cell appears to be a monocyte-derived macrophages because TC-G 1008 treatment suppressed lipopolysaccharide-induced IL-6 production from U937 macrophages in vitro. Taken together, GPR39 agonist TC-G 1008 ameliorates liver injury in the Con A model by blocking pro-inflammatory cytokine production. Use of GPR39 agonists for monotherapy or in combination with immunosuppressants might prove to be beneficial in the treatment of autoimmune hepatitis.

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G protein-coupled receptor 39 plays an anti-inflammatory role by enhancing IL-10 production from macrophages under inflammatory conditions

Cited by 23 publications

References 28 publications

Supramolecular Macrophage‐Liposome Marriage for Cell‐Hitchhiking Delivery and Immunotherapy of Acute Pneumonia and Melanoma

Supramolecular Macrophage‐Liposome Marriage for Cell‐Hitchhiking Delivery and Immunotherapy of Acute Pneumonia and Melanoma

Activation of GPR39 With TC-G 1008 Attenuates Neuroinflammation Via SIRT1/PGC-1α/Nrf2 Pathway Post Neonatal Hypoxic-ischemic Injury in Rats

G Protein-Coupled Receptor 39 Agonist Improves Concanavalin A-Induced Hepatitis in Mice

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