Expression of P2X4 receptor in rat C6 glioma by tumor-associated macrophages and activated microglia

Guo, Liang-Hao; Trautmann, Katrin; Schluesener, Hermann J.

doi:10.1016/j.jneuroim.2004.04.005

Cited by 32 publications

(28 citation statements)

References 22 publications

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“…P2X 4 receptor activation has been suggested to mediate synaptic transmission (North, 2002), and P2X 4 signaling may play a critical role in the inflammatory responses in the pathology of brain tumors, neuropathic pain, and multiple sclerosis (Guo et al, 2004(Guo et al, , 2006Guo and Schluesener, 2005;Ulmann et al, 2008). Our study shows that P2X 4 -KO animals have lower levels of caspase-1 activation and IL-1␤ cleavage, resulting in significant improvement in tissue sparing and functional recovery.…”

Section: Discussionmentioning

confidence: 50%

P2X₄Receptors Influence Inflammasome Activation after Spinal Cord Injury

Vaccari¹,

Bastien²,

Yurcisin³

et al. 2012

J. Neurosci.

161

141

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P2X 4 and P2X 7 are the predominant purinergic P2X receptor subtypes expressed on immune and neural cells. These receptor subtypes traffic between intracellular compartments and the plasma membrane and form protein interactions with each other to regulate ATPdependent signaling. Our recent studies have shown that P2X 7 receptors in neurons and astrocytes activate NLRP1 inflammasomes, but whether P2X 4 receptors regulate inflammasome signaling is essentially unknown. Here, we demonstrate that P2X 4 receptors are expressed in neurons of the spinal cord. We provide direct evidence that spinal cord injury (SCI) induces an innate inflammatory response that leads to increased caspase-l cleavage and

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Section: Discussionmentioning

confidence: 50%

P2X₄Receptors Influence Inflammasome Activation after Spinal Cord Injury

Vaccari¹,

Bastien²,

Yurcisin³

et al. 2012

J. Neurosci.

161

141

View full text Add to dashboard Cite

show abstract

“…Thus, targeting the P2X4R-p38 -MAPKsignaling pathway in spinal microglia could prove useful in the development of novel therapeutic approaches for treating pain hypersensitivity caused by nerve injury. In addition, involvement of microglial P2X4Rs reported after injury to a peripheral nerve is increasingly being found in other models of CNS pathology such as inflammation Zhang et al, 2008), CNS injury (Schwab et al, 2005;Zhang et al, 2006), and in glioblastoma brain tumors (Guo et al, 2004). Therefore, the implications of our findings may extend not only to pathological pain states but also to a diversity of CNS disorders.…”

Section: Discussionmentioning

confidence: 55%

P2X4-Receptor-Mediated Synthesis and Release of Brain-Derived Neurotrophic Factor in Microglia Is Dependent on Calcium and p38-Mitogen-Activated Protein Kinase Activation

Trang¹,

Beggs²,

Wan³

et al. 2009

J. Neurosci.

417

378

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Microglia in the dorsal horn of the spinal cord are increasingly recognized as being crucial in the pathogenesis of pain hypersensitivity after injury to a peripheral nerve. It is known that P2X4 purinoceptors (P2X4Rs) cause the release of brain-derived neurotrophic factor (BDNF) from microglia, which is necessary for maintaining pain hypersensitivity after nerve injury. However, there is a critical gap in understanding how activation of microglial P2X4Rs leads to the release of BDNF. Here, we show that stimulating P2X4Rs with ATP evokes a biphasic release of BDNF from microglia: an early phase occurs within 5 min, whereas a late phase peaks 60 min after ATP stimulation. Concomitant with the late phase of release is an increased level of BDNF within the microglia. Both phases of BDNF release and the accumulation within the microglia are dependent on extracellular Ca 2ϩ . The late phase of BDNF release and accumulation, but not the early phase of release, are suppressed by inhibiting transcription and translation, indicating that activation of P2X4R causes an initial release of a pre-existing pool of BDNF followed by an increase in de novo synthesis of BDNF. The release of BDNF is abolished by inhibiting SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor)-mediated exocytosis. Furthermore, we find that the P2X4R-evoked release and synthesis of BDNF are dependent on activation of p38-mitogen-activated protein kinase (MAPK). Together, our findings provide a unifying mechanism for pain hypersensitivity after peripheral nerve injury through P2X4R-evoked increase in Ca 2ϩ and activation of p38-MAPK leading to the synthesis and exocytotic release of BDNF from microglia.

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“…Microglia show altered P2X 4 R expression in response to multiple types of nervous system damage (24,25). However, peripheral tissue inflammation caused by intraplantar injection of complete Freund's adjuvant does not increase microglial P2X 4 R (13).…”

Section: P2x 4 Receptor (P2x 4 R)mentioning

confidence: 99%

Microglial Regulation of Neuropathic Pain

et al. 2013

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Abstract. Neuropathic pain is a highly debilitating chronic pain state that is a consequence of nerve injury or of diseases such as diabetes, cancer, infection, autoimmune disease, or trauma. Neuropathic pain is often resistant to currently available analgesics. There is a rapidly growing body of evidence indicating that signalings from spinal microglia play crucial roles in the pathogenesis of neuropathic pain. After peripheral nerve injury, microglia transform to reactive states through the expression of various genes such as cell-surface receptors (including purinergic receptors) and proinflammatory cytokines that enhance synaptic transmission in dorsal horn neurons. Inhibiting function or expression of these microglial molecules strongly suppresses pain hypersensitivity to innocuous mechanical stimuli (tactile allodynia), a hallmark symptom of neuropathic pain. A recent study also reveals that the transcription factor IRF8 (interferon regulatory factor 8) is a critical regulator of the nerve injury-induced gene expression in microglia. The present review article highlights the recent advances in our understanding of spinal microglia in neuropathic pain.

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Expression of P2X4 receptor in rat C6 glioma by tumor-associated macrophages and activated microglia

Cited by 32 publications

References 22 publications

P2X₄Receptors Influence Inflammasome Activation after Spinal Cord Injury

P2X₄Receptors Influence Inflammasome Activation after Spinal Cord Injury

P2X4-Receptor-Mediated Synthesis and Release of Brain-Derived Neurotrophic Factor in Microglia Is Dependent on Calcium and p38-Mitogen-Activated Protein Kinase Activation

Microglial Regulation of Neuropathic Pain

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Expression of P2X4 receptor in rat C6 glioma by tumor-associated macrophages and activated microglia

Cited by 32 publications

References 22 publications

P2X4Receptors Influence Inflammasome Activation after Spinal Cord Injury

P2X4Receptors Influence Inflammasome Activation after Spinal Cord Injury

P2X4-Receptor-Mediated Synthesis and Release of Brain-Derived Neurotrophic Factor in Microglia Is Dependent on Calcium and p38-Mitogen-Activated Protein Kinase Activation

Microglial Regulation of Neuropathic Pain

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P2X₄Receptors Influence Inflammasome Activation after Spinal Cord Injury

P2X₄Receptors Influence Inflammasome Activation after Spinal Cord Injury