Gene regulation of α4β2 nicotinic receptors: microarray analysis of nicotine-induced receptor up-regulation and anti-inflammatory effects

Vagal stimulation (VS) during myocardial ischemia and reperfusion has beneficial effects. However, it is not known whether short-term VS applied before ischemia or at the onset of reperfusion protects the ischemic myocardium. This study was designed to determine whether short-term VS applied before ischemia or at the onset of reperfusion reduces myocardial infarct size (IS), mimicking classic preconditioning and postconditioning. A second objective was to study the participation of muscarinic and nicotinic receptors in the protection of both preischemic and reperfusion stimulation. FVB mice were subjected to 30 min of regional myocardial ischemia followed by 2 h of reperfusion without VS, with 10-min preischemic VS (pVS), or with VS during the first 10 min of reperfusion (rVS). pVS reduced IS, and this effect was abolished by atropine and wortmannin. rVS also reduced IS in a similar manner, and this effect was abolished by the α7-nicotinic acetylcholine receptor blocker methyllycaconitine. pVS increased Akt and glycogen synthase kinase (GSK)-3β phosphorylation. No changes in Akt and GSK-3β phosphorylation were observed in rVS. Stimulation-mediated IS protection was abolished with the JAK2 blocker AG490. rVS did not modify IL-6 and IL-10 levels in the plasma or myocardium. Splenic denervation and splenectomy did not abolish the protective effect of rVS. In conclusion, pVS and rVS reduced IS by different mechanisms: pVS activated the Akt/GSK-3β muscarinic pathway, whereas rVS activated α7-nicotinic acetylcholine receptors and JAK2, independently of the cholinergic anti-inflammatory pathway. NEW & NOTEWORTHY Our data suggest, for the first time, that vagal stimulation applied briefly either before ischemia or at the beginning of reperfusion mimics classic preconditioning and postconditioning and reduces myocardial infarction, activating different mechanisms. We also infer an important role of α7-nicotinic receptors for myocardial protection independent of the cholinergic anti-inflammatory pathway.

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Apical splenic nerve electrical stimulation discloses an anti-inflammatory pathway relying on adrenergic and nicotinic receptors in myeloid cells

Brain Behavior and Immunity ◽

10.1016/j.bbi.2019.03.015 ◽

2019 ◽

Vol 80 ◽

pp. 238-246 ◽

Cited By ~ 10

Author(s):

Mélanie Guyot ◽

Thomas Simon ◽

Clara Panzolini ◽

Franck Ceppo ◽

Douglas Daoudlarian ◽

...

Keyword(s):

Electrical Stimulation ◽

Nicotinic Receptors ◽

Myeloid Cells ◽

Inflammatory Pathway ◽

Anti Inflammatory

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Microarray analysis of human umbilical vein endothelial cells highlights new anti-inflammatory and vasodilating properties of the omega-3 fatty acid docosahexaenoic acid

European Heart Journal ◽

10.1093/eurheartj/eht309.p4157 ◽

2013 ◽

Vol 34 (suppl 1) ◽

pp. P4157-P4157

Author(s):

M. Massaro ◽

E. Scoditti ◽

M. A. Carluccio ◽

R. Martinelli ◽

T. Buonuomo ◽

...

Keyword(s):

Endothelial Cells ◽

Fatty Acid ◽

Docosahexaenoic Acid ◽

Microarray Analysis ◽

Umbilical Vein ◽

Omega 3 ◽

Human Umbilical Vein ◽

Omega 3 Fatty Acid ◽

Anti Inflammatory ◽

Umbilical Vein Endothelial Cells

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DNA microarray analysis reveals a role for lysophosphatidic acid in the regulation of anti-inflammatory genes in MC3T3-E1 cells

Bone ◽

10.1016/j.bone.2007.06.029 ◽

2007 ◽

Vol 41 (5) ◽

pp. 833-841 ◽

Cited By ~ 11

Author(s):

Katrina M. Waters ◽

Ruimin Tan ◽

Damian C. Genetos ◽

Seema Verma ◽

Clare E. Yellowley ◽

...

Keyword(s):

Microarray Analysis ◽

Dna Microarray ◽

Lysophosphatidic Acid ◽

Inflammatory Genes ◽

Dna Microarray Analysis ◽

Anti Inflammatory

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Spinal neuronal excitability and neuroinflammation in a model of chemotherapeutic neuropathic pain: targeting the resolution pathways

Journal of Neuroinflammation ◽

10.1186/s12974-020-01997-w ◽

2020 ◽

Vol 17 (1) ◽

Cited By ~ 1

Author(s):

Pongsatorn Meesawatsom ◽

Gareth Hathway ◽

Andrew Bennett ◽

Dumitru Constantin-Teodosiu ◽

Victoria Chapman

Keyword(s):

Neuropathic Pain ◽

Dorsal Horn ◽

Microarray Analysis ◽

Dynamic Range ◽

Evoked Responses ◽

Sprague Dawley ◽

Resolvin D1 ◽

Post Discharge ◽

Critical Feature ◽

Anti Inflammatory

Abstract Background Neuroinflammation is a critical feature of sensitisation of spinal nociceptive processing in chronic pain states. We hypothesised that the resolvin pathways, a unique endogenous control system, may ameliorate aberrant spinal processing of somatosensory inputs associated with chemotherapy-induced neuropathic pain (CINP). Method The paclitaxel (PCX) model of CINP was established in male Sprague-Dawley rats and compared to control rats (n = 23 and 22, respectively). Behavioural pain responses were measured, and either single unit electrophysiological recordings of dorsal horn wide dynamic range (WDR) neurones were performed, or mRNA microarray analysis of the dorsal horn of the spinal cord was undertaken. Results PCX rats exhibited significant changes in behavioural responses to mechanical and cold stimuli. A higher proportion of WDR neurones in PCX rats were polymodal (generating post-discharge following a non-noxious mechanical stimulus, responding to non-noxious cold and exhibiting spontaneous activity) compared to control (p < 0.05). Microarray analysis revealed changes in proinflammatory pathways (Tlr, Tnfrsf1a, Nlrp1a, Cxcr1, Cxcr5, Ccr1, Cx3cr1) and anti-inflammatory lipid resolvin pathways (Alox5ap, Cyp2j4 and Ptgr1) compared to control (p < 0.05). Ingenuity pathway analysis predicted changes in glutamatergic and astrocyte signaling in the PCX group. Activation of the resolvin system via the spinal administration of aspirin-triggered resolvin D1 (AT-RvD1) markedly inhibited (73 ± 7% inhibition) normally non-noxious mechanically (8 g) evoked responses of WDR neurones only in PCX rats, whilst leaving responses to noxious mechanically induced stimuli intact. Inhibitory effects of AT-RvD1were comparable in magnitude to spinal morphine (84 ± 4% inhibition). Conclusion The PCX model of CINP was associated with mechanical allodynia, altered neuronal responses and dysregulation of pro- and anti-inflammatory signalling in the spinal dorsal horn. The resolvin AT-RvD1 selectively inhibited low weight mechanical-evoked responses of WDR neurones in PCX rats, but not in controls. Our data support the targeting of spinal neuroinflammation via the activation of the resolvin system as a new therapeutic approach for CINP.

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