Purinergic receptor P2X7: A novel target for anti-inflammatory therapy

Mehta, Nisha; Kaur, Maninder; Singh, Manjinder; Chand, Sukhvir; Vyas, Bhawna; Silakari, Pragati; Bahia, Malkeet Singh; Silakari, Om

doi:10.1016/j.bmc.2013.10.054

Cited by 95 publications

(82 citation statements)

References 152 publications

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“…P2X 7 receptor is involved in the regulation of inflammation [8,12] and plays a significant role in the regulation of the immune system [13]. Absence of P2X 7 receptor (P2X 7 knockout mice) leads to an inability to release IL-1β in response to ATP stimulation from peritoneal macrophages [14].…”

Section: Discussionmentioning

confidence: 99%

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P2X7 Receptor Expression in Peripheral Blood Monocytes Is Correlated With Plasma C-Reactive Protein and Cytokine Levels in Patients With Type 2 Diabetes Mellitus: a Preliminary Report

Nie

Xiong

et al. 2015

Inflammation

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Chronic inflammation plays a major role in development of type 2 diabetes mellitus (T2DM). C-reactive protein (CRP) and inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) are directly involved in the occurrence of insulin resistance. Increased extracellular ATP levels can amplify the inflammatory response in vivo via the P2X7 receptor. The present study aimed to assess the relationship between P2X7 receptor expression in human peripheral blood monocytes and plasma levels of TNF-α, IL-1β, and CRP in T2DM patients. The results showed the association of increased P2X7 receptor expression of monocytes with high serum CRP, TNF-α, and IL-1β levels. TNF-α and IL-1β levels were lowest in healthy subjects; in T2DM patients, these inflammatory markers were less abundant in individuals with normal CRP levels compared to those with high CRP contents. In contrast, IL-10 levels in T2DM patients with high CRP levels were dramatically decreased. P2X7 receptor expression in monocytes from T2DM patients with high CRP levels was significantly increased in comparison with healthy individuals and T2DM patients with normal CRP levels. These findings indicated that P2X7 receptor in peripheral blood monocytes may be involved in the pathological changes of T2DM, particularly affecting patients with high CRP levels.

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Section: Discussionmentioning

confidence: 99%

“…There are two P2 receptor subfamilies, P2X cation channel-and P2Y G-proteincoupled receptors. At least eight P2Y family members (P2Y 1-2 , P2Y 4 , P2Y 6 , P2Y [11][12][13][14] and seven P2X receptors (P2X 1-7 ) have been described. P2X 7 receptor induction has been implicated in a variety of inflammatory conditions [8].…”

Section: Introductionmentioning

confidence: 99%

P2X7 Receptor Expression in Peripheral Blood Monocytes Is Correlated With Plasma C-Reactive Protein and Cytokine Levels in Patients With Type 2 Diabetes Mellitus: a Preliminary Report

Nie

Xiong

et al. 2015

Inflammation

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“…P2X7 receptor antagonists are promising targets for antiinflammatory therapy [125,126], including inflammation in the CNS [11,95,100,127,128]. In view of its potent proinflammatory effect, the analgesic activity of P2X7 receptor blockers is of interest for therapeutic implications [99].…”

Section: Therapeutic Potentialmentioning

confidence: 99%

P2X ion channel receptors and inflammation

Burnstock

2016

Purinergic Signalling

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Neuroinflammation limits tissue damage in response to pathogens or injury and promotes repair. There are two stages of inflammation, initiation and resolution. P2X receptors are gaining attention in relation to immunology and inflammation. The P2X7 receptor in particular appears to be an essential immunomodulatory receptor, although P2X1 and P2X4 receptors also appear to be involved. ATP released from damaged or infected cells causes inflammation by release of inflammatory cytokines via P2X7 receptors and acts as a danger signal by occupying upregulated P2X receptors on immune cells to increase immune responses. The purinergic involvement in inflammation is being explored for the development of novel therapeutic strategies.

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“…The pathogenesis of myocardial ischemia is associated with the balance of anti-and pro-inflammatory cytokines [48,50]. P2X 7 receptors play a significant role in inflammatory diseases [11,16,17,46,47]. Pharmacological inhibition of P2X 7 receptors attenuates inflammatory diseases [11,46,47,55,56].…”

Section: Discussionmentioning

confidence: 99%

LncRNA NONRATT021972 involved the pathophysiologic processes mediated by P2X7 receptors in stellate ganglia after myocardial ischemic injury

Zou

Xie

et al. 2015

Purinergic Signalling

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Adenosine triphosphate (ATP) acts on P2X receptors to initiate signal transmission. P2X 7 receptors play a role in the pathophysiological process of myocardial ischemic injury. Long noncoding RNAs (lncRNAs) participate in numerous biological functions independent of protein translation. LncRNAs are implicated in nervous system diseases. This study investigated the effects of NONRATT021972 small interference RNA (siRNA) on the pathophysiologic processes mediated by P2X 7 receptors in stellate ganglia (SG) after myocardial ischemic injury. Our results demonstrated that the expression of NONRATT021972 in SG was significantly higher in the myocardial ischemic (MI) group than in the control group. Treatment of MI rats with NONRATT021972 siRNA, the P2X 7 antagonist brilliant blue G (BBG), or P2X 7 siRNA improved the histology of injured ischemic cardiac tissues and decreased the elevated concentrations of serum myocardial enzymes, creatine kinase (CK), CK isoform MB (CK-MB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) compared to the MI rats. NONRATT021972 siRNA, BBG, or P2X 7 siRNA treatment in MI rats decreased the expression levels of P2X 7 immunoreactivity, P2X 7 messenger RNA (mRNA), and P2X 7 protein, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and phosphorylated p38 mitogenactivated protein kinase (p38 MAPK) in the SG compared to MI rats. NONRATT021972 siRNA treatment prevented the pathophysiologic processes mediated by P2X 7 receptors in the SG after myocardial ischemic injury.

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Purinergic receptor P2X7: A novel target for anti-inflammatory therapy

Cited by 95 publications

References 152 publications

P2X7 Receptor Expression in Peripheral Blood Monocytes Is Correlated With Plasma C-Reactive Protein and Cytokine Levels in Patients With Type 2 Diabetes Mellitus: a Preliminary Report

P2X7 Receptor Expression in Peripheral Blood Monocytes Is Correlated With Plasma C-Reactive Protein and Cytokine Levels in Patients With Type 2 Diabetes Mellitus: a Preliminary Report

P2X ion channel receptors and inflammation

LncRNA NONRATT021972 involved the pathophysiologic processes mediated by P2X7 receptors in stellate ganglia after myocardial ischemic injury

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