IL-1β induces murine airway 5-HT2A receptor hyperresponsiveness via a non-transcriptional MAPK-dependent mechanism

Zhang, Yaping; Cardell, Lars-Olaf; Adner, Mikael

doi:10.1186/1465-9921-8-29

Cited by 35 publications

(23 citation statements)

References 35 publications

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“…Activated macrophages release IL-1␤ and TNF-␣, both of which are associated with asthma and airway hyperresponsiveness (2,7,29,57) and have been shown to decrease M2 receptor expression (35). This study supports the hypothesis that release of TNF-␣ from alveolar macrophages mediates parathion-induced airway hyperreactivity.…”

Section: Discussionsupporting

confidence: 81%

“…Macrophages release TNF-␣ and IL-1␤, both of which are increased in the lungs of asthmatics and in animal models of hyperreactivity (5,7). In experimental models, administration of TNF-␣ or IL-1␤ enhances airway reactivity (29,57). Conversely, blocking TNF-␣ or IL-1␤ with specific antagonists prevents airway hyperreactivity caused by antigen and other environmental triggers, such as ozone (35,49,56).…”

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confidence: 96%

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Macrophage TNF-α mediates parathion-induced airway hyperreactivity in guinea pigs

Proskocil

Bruun

Jacoby

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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Organophosphorus pesticides (OPs) are implicated in human asthma. We previously demonstrated that, at concentrations that do not inhibit acetylcholinesterase activity, the OP parathion causes airway hyperreactivity in guinea pigs as a result of functional loss of inhibitory M2 muscarinic receptors on parasympathetic nerves. Because macrophages are associated with asthma, we investigated whether macrophages mediate parathion-induced M2 receptor dysfunction and airway hyperreactivity. Airway physiology was measured in guinea pigs 24 h after a subcutaneous injection of parathion. Pretreatment with liposome-encapsulated clodronate induced alveolar macrophage apoptosis and prevented parathion-induced airway hyperreactivity in response to electrical stimulation of the vagus nerves. As determined by qPCR, TNF-α and IL-1β mRNA levels were increased in alveolar macrophages isolated from parathion-treated guinea pigs. Parathion treatment of alveolar macrophages ex vivo did not significantly increase IL-1β and TNF-α mRNA but did significantly increase TNF-α protein release. Consistent with these data, pretreatment with the TNF-α inhibitor etanercept but not the IL-1β receptor inhibitor anakinra prevented parathion-induced airway hyperreactivity and protected M2 receptor function. These data suggest a novel mechanism of OP-induced airway hyperreactivity in which low-level parathion activates macrophages to release TNF-α-causing M2 receptor dysfunction and airway hyperreactivity. These observations have important implications regarding therapeutic approaches for treating respiratory disease associated with OP exposures.

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Section: Discussionsupporting

confidence: 81%

mentioning

confidence: 96%

Macrophage TNF-α mediates parathion-induced airway hyperreactivity in guinea pigs

Proskocil

Bruun

Jacoby

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…5-HT induces activation of 5-HT 2A receptors and results in bronchoconstriction [21] . Inhaled 5-HT has no consistent effect on airway contraction in either normal or asthmatic subjects [22] .…”

Section: Discussionmentioning

confidence: 99%

Alteration of airway responsiveness mediated by receptors in ovalbumin-induced asthmatic E3 rats

Yang

Cao

et al. 2009

Acta Pharmacol Sin

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Aim: Airway hyperresponsiveness is a constant feature of asthma. The aim of the present study was to investigate airway hyperreactivity mediated by contractile and dilative receptors in an ovalbumin (OVA)-induced model of rat asthma. Methods: Asthmatic E3 rats were prepared by intraperitoneal injection with OVA/aluminum hydroxide and then challenged with intranasal instillation of OVA-PBS two weeks later. The myograph method was used to measure the responses of constriction and dilatation in the trachea, main bronchi and lobar bronchi. Results: In asthmatic E3 rats, β 2 adrenoceptor-mediated relaxation of airway smooth muscle pre-contracted with 5-HT was inhibited, and there were no obvious difference in relaxation compared with normal E3 rats. Contraction of lobar bronchi mediated by 5-HT and sarafotoxin 6c was more potent than in the trachea or main bronchi. Airway contractions mediated by the endothelin (ET) A receptor, ET B receptor and M 3 muscarinic receptor were augmented, and the augmented contraction was most obvious in lobar bronchi. The order of efficacy of contraction for lobar bronchi induced by agonists was ET-1, sarafotoxin 6c>ACh>5-HT. OX8 (an antibody against CD8 + T cells) strongly shifted and OX35 (an antibody against CD4 + T cells) modestly shifted isoprenaline-induced concentration-relaxation curves in a nonparallel fashion to the left with an increased R max in asthmatic rats and sarafotoxin 6c-induced concentration-contractile curves to the right with a decreased E max . Conclusion: The inhibition of airway relaxation and the augmentation of contraction mediated by receptors contribute to airway hyperresponsiveness and involve CD8 + and CD4 + T cells.

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“…Long-standing systemic inflammation may give rise to altered expression of certain receptors, including possibly 5-HT2AR, whose expression was reported to be substantially increased on CD3 positive T cells and in the vessels from involved skin in psoriasis patients [26]. Persistent (7 days) exposure to the pro-inflammatory cytokine IL-β in murine tracheal rings in vitro was reported to increase 5-HT2AR-mediated airway muscle contractility [27]. The 5-HT2AR was also reported to have played a role in sustained, increased nitric oxide production in animal models of LPS-induced inflammation [28,29].…”

Section: Discussionmentioning

confidence: 99%

Circulating Neurotoxic 5-HT2A Receptor Agonist Autoantibodies in Adult Type 2 Diabetes with Parkinson’s Disease

Zimering¹

2018

JED

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Aims: To test whether circulating neurotoxic autoantibodies increase in adult type 2 diabetes mellitus with Parkinson's disease (PD) or dementia. To identify the G-protein coupled receptor on neuroblastoma cells mediating neural inhibitory effects in diabetic Parkinson's disease plasma autoantibodies. To determine the mechanism of accelerated neuroblastoma cell death and acute neurite retraction induced by diabetic Parkinson's disease and dementia autoantibodies.Methods: Protein-A eluates from plasma of twelve older adult male diabetic patients having Parkinson's disease (n=10) or dementia (n=2), and eight age-matched control diabetic patients were tested for ability to cause accelerated N2A neuroblastoma cell death and acute neurite retraction. Specific antagonists of G protein coupled receptors belonging to the G alpha q subfamily of heterotrimetric G-proteins, the phospholipase C/inositol triphosphate/Ca2+ pathway, or the RhoA/Rho kinase pathway were tested for ability to block diabetic Parkinson's disease/dementia autoantibodyinduced neurite retraction or N2A accelerated cell loss. Sequential Liposorber LA-15 dextran sulfate cellulose/protein-A affinity chromatography was used to obtain highly-purified fractions of diabetic Parkinson's disease autoantibodies .Results: Mean accelerated neuroblastoma cell loss induced by diabetic Parkinson's disease or dementia autoantibodies significantly exceeded (P = 0.001) the level of N2A cell loss induced by an identical concentration of the diabetic autoantibodies in control patients without these two comorbid neurodegenerative disorders. Co-incubation of diabetic Parkinson's disease and dementia autoantibodies with two-hundred nanomolar concentrations of M100907, a highly selective 5-HT2AR antagonist, completely prevented autoantibody-induced accelerated N2A cell loss and neurite retraction. A higher concentration (500 nM-10μM) of alpha-1 adrenergic, angiotensin II type 1, or endothelin A receptor antagonists did not substantially inhibit autoantibody-induced neuroblastoma cell death or prevent neurite retraction. Antagonists of the inositol triphosphate receptor (2-APB, 50μM), the intracellular calcium chelator (BAPTA-AM, 30 μM) and Y27632 (10 μM), a selective RhoA/Rho kinase inhibitor, each completely blocked acute neurite retraction induced by sixty nanomolar concentrations of diabetic Parkinson's disease autoantibodies. Co-incubation with 2-APB (1-2 μM) for 8 hours' prevented autoantibody-induced N2A cell loss. The highly-purified fraction obtained after Liposorber LA/protein-A affinity chromatography in hypertriglyceridemic diabetic dementia and Parkinson's disease plasmas had apparent MWs > 30 kD, and displayed enhanced N2A toxicity requiring substantially higher concentrations of 5-HT2AR antagonists (M100907, ketanserin, spiperone) to effectively neutralize. Conclusion:These data suggest increased autoantibodies in older adult diabetes with Parkinson's disease or dementia cause accelerated neuron loss via the 5-hydroxytryptamine 2 receptor coupled to ino...

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IL-1β induces murine airway 5-HT2A receptor hyperresponsiveness via a non-transcriptional MAPK-dependent mechanism

Cited by 35 publications

References 35 publications

Macrophage TNF-α mediates parathion-induced airway hyperreactivity in guinea pigs

Macrophage TNF-α mediates parathion-induced airway hyperreactivity in guinea pigs

Alteration of airway responsiveness mediated by receptors in ovalbumin-induced asthmatic E3 rats

Circulating Neurotoxic 5-HT2A Receptor Agonist Autoantibodies in Adult Type 2 Diabetes with Parkinson’s Disease

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