Functional characterization of purinergic receptor P2Y14 in the Japanese flounder (Paralichthys olivaceus) head kidney macrophages

Li, Shuo; Wang, Nan; Feng, Yifei; Li, Jiafang; Geng, Xin; Sun, Jinsheng

doi:10.1016/j.fsi.2019.07.053

Cited by 7 publications

(2 citation statements)

References 35 publications

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“…Upon activation, P2Y 14 R inhibits adenylyl cyclase for the synthesis of cAMP, a second messenger participating in the signaling of various immune events such as inflammatory cytokine expression/secretion and pyroptosis ( 70 , 71 ). In flounder, P2Y 14 R was reported to be involved in the inflammatory signaling ( 72 ). In the present work, we discovered that during E. tarda infection, L-methionine and UDP-glucose levels were significantly lower at 23°C than at 15°C, and exogenously added L-methionine and UDP-glucose effectively attenuated the infectivity of E. tarda and induced the expression of the proinflammatory cytokines of TNF-α, IL-1β, IL-6 and IL-27β.…”

Section: Discussionmentioning

confidence: 99%

Temperature induces metabolic reprogramming in fish during bacterial infection

Sun

Zhang

et al. 2022

Front. Immunol.

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Water temperature elevation as a consequence of global warming results in increased incidence of bacterial disease, such as edwardsiellosis, in fish farming. Edwardsiellosis is caused by the bacterial pathogen Edwardsiella tarda and affects many farmed fish including flounder (Paralichthys olivaceus). Currently, the effect of temperature on the metabolic response of flounder to E. tarda infection is unclear. In this study, we found that compared to low temperature (15°C), high temperature (23°C) enhanced E. tarda dissemination in flounder tissues. To examine the impact of temperature on the metabolism of flounder induced by E. tarda, comparative metabolomics were performed, which identified a large number of metabolites responsive to E. tarda invasion and temperature alteration. During E. tarda infection, the metabolic profile induced by elevated temperature was mainly featured by extensively decreased amino acids and TCA intermediates such as succinate, a proven immune regulator. Further, 38 potential metabolite markers of temperature effect (MMTE) in association with bacterial infection were identified. When used as exogenous supplements, two of the MMTE, i.e., L-methionine and UDP-glucose, effectively upregulated the expression of pro-inflammatory cytokines and suppressed E. tarda infection in flounder leukocytes. Taken together, the results of this study indicate an important influence of temperature on the metabolism of flounder during bacterial infection, which eventually affects the survivability of the fish.

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Section: Discussionmentioning

confidence: 99%

Temperature induces metabolic reprogramming in fish during bacterial infection

Sun

Zhang

et al. 2022

Front. Immunol.

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“…As a family of purinergic receptors, P2Y receptors (P2YRs) belong to the G protein-coupled receptor (GPCR) superfamily. Among them, GPR105, also known as P2Y 14 receptor, could be activated by uridine diphosphate glucose sugars (UDP-sugars) to inhibit adenylate cyclase (AC)-mediated cAMP production via Gi/o-coupled protein ( 10 ), which was regarded to be involved in the modulation of immune inflammatory stress ( 11 , 12 ). Recent studies proposed that MSU induced an upregulated GPR105 expression with a significant elevation in the secretion of inflammatory cytokines in human epidermal keratinocytes (NHEKs), intimating the roles of GPR105 in immune inflammatory responses exposed to MSU ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

GPR105-Targeted Therapy Promotes Gout Resolution as a Switch Between NETosis and Apoptosis of Neutrophils

et al. 2022

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The fate of infiltrating neutrophils in inflamed joints determines the development of acute gouty arthritis (AGA). GPR105 highly expressed in human neutrophils is sensitive to monosodium urate crystals (MSU); nevertheless, the roles of GPR105 in AGA remain unclear. Here, we show that GPR105 is significantly upregulated in peripheral polymorphonuclear neutrophils of AGA patients. GPR105 knockout (GPR105−/−) prevented NETosis and induced apoptosis of neutrophils under MSU exposure, as well as attenuating inflammatory cascades in AGA. Mechanistically, GPR105 deletion activated cAMP-PKA signals, thereby disrupting Raf-Mek1/2-Erk1/2 pathway-mediated NADPH oxidase activation, contributing to inhibition of NETosis. Whereas, cAMP-PKA activation resulting in GPR105 deficiency modulated PI3K-Akt pathway to regulate apoptosis. More importantly, suppression of cAMP-PKA pathway by SQ22536 and H-89 restored NETosis instead of apoptosis in GPR105−/− neutrophils, promoting MSU-induced gout flares. Interestingly, lobetyolin was screened out as a potent GPR105 antagonist using molecular docking-based virtual screening and in vitro activity test, which efficiently attenuated MSU-induced inflammatory response interacting with GPR105. Taken together, our study implicated that modulating cell death patterns between NETosis and apoptosis through targeting GPR105 could be a potential therapeutic strategy for the treatment of AGA.

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Extracellular ATP-mediated purinergic immune signaling in teleost fish: A review

Zhang

Feng

et al. 2021

Aquaculture

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Functional characterization of purinergic receptor P2Y14 in the Japanese flounder (Paralichthys olivaceus) head kidney macrophages

Cited by 7 publications

References 35 publications

Temperature induces metabolic reprogramming in fish during bacterial infection

Temperature induces metabolic reprogramming in fish during bacterial infection

GPR105-Targeted Therapy Promotes Gout Resolution as a Switch Between NETosis and Apoptosis of Neutrophils

Extracellular ATP-mediated purinergic immune signaling in teleost fish: A review

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