Sphingosine-1-phosphate induces migration of microglial cells via activation of volume-sensitive anion channels, ATP secretion and activation of purinergic receptors

Chronic pain imposes a tremendous burden on the sufferer’s quality of life. Mounting evidence supports a critical role for neuroimmune interactions in the development and maintenance of chronic pain. Nerve injury leads to the activation of glia via sphingosine-1-phosphate, Toll-like receptors, chemokines, neuropeptides, and purinergic receptors. In turn, activated glia influence neuronal activity via interleukin 1β, tumor necrosis factor, brain-derived neurotrophic factor, reactive oxygen species, and excitatory amino acids. Epigenetic mechanisms of neuroimmune communication are also discussed. Investigation of neuroimmune interactions after peripheral nerve injury broadens our understanding of the mechanisms that drive neuropathic pain, and such interactions provide potential therapeutic targets for managing neuropathic pain.

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Purinergic receptors on microglial cells: functional expression in acute brain slices and modulation of microglial activationin vitro

European Journal of Neuroscience ◽

10.1046/j.1460-9568.2003.02663.x ◽

2003 ◽

Vol 17 (11) ◽

pp. 2267-2276 ◽

Cited By ~ 148

Author(s):

Clemens Boucsein ◽

Robert Zacharias ◽

Katrin Färber ◽

Sanja Pavlovic ◽

Uwe-Karsten Hanisch ◽

...

Keyword(s):

Purinergic Receptors ◽

Brain Slices ◽

Functional Expression ◽

Microglial Cells

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Selective Upregulation of Per1 mRNA Expression by ATP Through Activation of P2X7 Purinergic Receptors Expressed in Microglial Cells

Journal of Pharmacological Sciences ◽

10.1254/jphs.11069fp ◽

2011 ◽

Vol 116 (4) ◽

pp. 350-361 ◽

Cited By ~ 25

Author(s):

Ryota Nakazato ◽

Takeshi Takarada ◽

Tomomi Yamamoto ◽

Shogo Hotta ◽

Eiichi Hinoi ◽

...

Keyword(s):

Mrna Expression ◽

Purinergic Receptors ◽

Microglial Cells

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Cross talk between P2 purinergic receptors modulates extracellular ATP-mediated interleukin-10 production in rat microglial cells

Experimental & Molecular Medicine ◽

10.3858/emm.2008.40.1.19 ◽

2008 ◽

Vol 40 (1) ◽

pp. 19 ◽

Cited By ~ 23

Author(s):

Dong Reoyl Seo ◽

Soo Yoon Kim ◽

Kyung You Kim ◽

Hwan Goo Lee ◽

Ju Hyun Moon ◽

...

Keyword(s):

Cross Talk ◽

Purinergic Receptors ◽

Interleukin 10 ◽

Extracellular Atp ◽

Microglial Cells ◽

P2 Purinergic Receptors

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Sphingosine-1-Phosphate Induces ATP Release via Volume-Regulated Anion Channels in Breast Cell Lines

Life ◽

10.3390/life11080851 ◽

2021 ◽

Vol 11 (8) ◽

pp. 851 ◽

Cited By ~ 1

Author(s):

Kishio Furuya ◽

Hiroaki Hirata ◽

Takeshi Kobayashi ◽

Masahiro Sokabe

Keyword(s):

Cell Lines ◽

Cultured Cells ◽

Imaging System ◽

Atp Release ◽

Cancer Microenvironment ◽

Anion Channels ◽

Breast Cell Lines ◽

Undifferentiated Cells ◽

Sphingosine 1 Phosphate ◽

Dose Dependent

High interstitial level of ATP and its lysate adenosine in the cancer microenvironment are considered a halo mark of cancer. Adenosine acts as a strong immune suppressor. However, the source of ATP release is unclear. We clarified the release of ATP via volume-regulated anion channels (VRACs) in breast cell lines using an ATP luminescence imaging system. We detected a slowly rising diffuse pattern of ATP release that was only observed in undifferentiated cells, not in differentiated primary cultured cells. This was confirmed by suppression with DCPIB, a blocker of VRACs, and shRNA for LRRC8A, an indispensable subunit of VRACs. We herein demonstrated that the inflammatory mediator sphingosine-1-phosphate (S1P), which exists abundantly in the cancer microenvironment, induced a diffuse pattern of ATP release isovolumetrically. The response was dose-dependent and suppressed by the knock-down of LRRC8A. It was also suppressed by blockers of S1P receptor 1 and 2 (W146 and JTE013, respectively). RTqPCR demonstrated the prominent presence of S1PR1 and S1PR2 mRNAs. We discussed the roles of S1P-induced ATP release in the cancer microenvironment.

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