Synergy between Tumor Necrosis Factor α and Interleukin 1β in Inducing Transcriptional Down-regulation of Muscarinic M2 Receptor Gene Expression

Haddad, El-Bdaoui; Rousell, Jonathan; Lindsay, Mark A.; Barnes, Peter J.

doi:10.1074/jbc.271.51.32586

Cited by 59 publications

(31 citation statements)

References 46 publications

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“…However, mechanisms of hyperreactivity 3 days after ozone exposure are not understood. Although IL-1b decreases M 2 receptor expression (56), this is unlikely to explain the ability of the IL-1 receptor antagonist to prevent airway hyperreactivity 3 days after ozone exposure, since we have previously shown that restoring M 2 receptor function at this time point does not prevent airway hyperreactivity (3).…”

Section: Discussionmentioning

confidence: 96%

IL-1 Receptors Mediate Persistent, but Not Acute, Airway Hyperreactivity to Ozone in Guinea Pigs

Verhein¹,

Jacoby

Fryer

2008

Am J Respir Cell Mol Biol

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Ozone exposure in the lab and environment causes airway hyperreactivity lasting at least 3 days in humans and animals. In guinea pigs 1 day after ozone exposure, airway hyperreactivity is mediated by eosinophils that block neuronal M 2 muscarinic receptor function, thus increasing acetylcholine release from airway parasympathetic nerves. However, mechanisms of ozone-induced airway hyperreactivity change over time, so that depleting eosinophils 3 days after ozone makes airway hyperreactivity worse rather than better. Ozone exposure increases IL-1b in bone marrow, which may contribute to acute and chronic airway hyperreactivity. To test whether IL-1b mediates ozone-induced airway hyperreactivity 1 and 3 days after ozone exposure, guinea pigs were pretreated with an IL-1 receptor antagonist (anakinra, 30 mg/kg, intraperitoneally) 30 minutes before exposure to filtered air or to ozone (2 ppm, 4 h). One or three days after exposure, airway reactivity was measured in anesthetized guinea pigs. The IL-1 receptor antagonist prevented ozoneinduced airway hyperreactivity 3 days, but not 1 day, after ozone exposure. Ozone-induced airway hyperreactivity was vagally mediated, since bronchoconstriction induced by intravenous acetylcholine was not changed by ozone. The IL-1 receptor antagonist selectively prevented ozone-induced reduction of eosinophils around nerves and prevented ozone-induced deposition of extracellular eosinophil major basic protein in airways. These data demonstrate that IL-1 mediates ozone-induced airway hyperreactivity at 3 days, but not 1 day, after ozone exposure. Furthermore, preventing hyperreactivity was accompanied by decreased eosinophil major basic protein deposition within the lung, suggesting that IL-1 affects eosinophil activation 3 days after ozone exposure.

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Section: Discussionmentioning

confidence: 96%

IL-1 Receptors Mediate Persistent, but Not Acute, Airway Hyperreactivity to Ozone in Guinea Pigs

Verhein¹,

Jacoby

Fryer

2008

Am J Respir Cell Mol Biol

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“…The muscarinic M 3 receptor expression was increased, whereas muscarinic M 2 receptor (M 2 ) resulted decreased, in induced sputum cells (macrophages, neutrophils, eosinophils) from COPD subjects compared with controls and control smokers (Profita et al, 2005). In this context, it has been observed that cytokines involved in COPD, such as interleukin (IL)-1␤ and tumor necrosis factor (TNF)-␣ (Chung, 2001), are able to downregulate synergistically the M 2 expression in human embryonic lung fibroblasts (HeLa 299 cells), whereas there is no evidence on the role of cytokines in the modification of muscarinic M 1 receptor (M 1 ), M 3 , and ChAT expression (Haddad et al, 1996). Moreover, the role of cigarette smoke (CS) on the expression of ChAT and MRs has to be clarified.…”

mentioning

confidence: 99%

“…IL-1␤ and TNF-␣ are involved in COPD (Chung, 2001) and have been demonstrated to generate a down-regulation of M 2 in human embryonic lung fibroblasts (HeLa 299 cells) (Haddad et al, 1996). Our findings that M 2 expression is reduced in fibroblasts from patients with COPD, compared with control smoker and control subjects, and that TNF-␣ is able to contribute to the M 2 down-regulation are consistent with these observations and support the concept of the involvement of ACh and MRs in the inflammatory processes in COPD.…”

Section: Muscarinic Receptor and Fibroblast Proliferation In Copd 761mentioning

confidence: 99%

Smoke, Choline Acetyltransferase, Muscarinic Receptors, and Fibroblast Proliferation in Chronic Obstructive Pulmonary Disease

Profita¹,

Bonanno²,

Siena³

et al. 2009

J Pharmacol Exp Ther

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Acetylcholine (ACh), synthesized by choline acetyltransferase (ChAT), and muscarinic M 1 , M 2 , and M 3 receptors (MRs) are involved in fibroblast proliferation. We evaluated ChAT, MRs, and extracellular signal-regulated kinase (ERK) 1/2 and nuclear factor (NF) B activation in lung fibroblasts from patients with chronic obstructive pulmonary disease (COPD), control smokers, and controls. Human fetal lung fibroblasts (HFL-1) stimulated with interleukin (IL)-1␤, tumor necrosis factor (TNF)-␣, and cigarette smoke extracts (CSEs) were evaluated for ChAT and MR expression. We tested the effects of ACh on fibroblast proliferation and its ability to bind fibroblasts from patients with COPD, control smokers, controls, and HFL-1 stimulated with IL-1␤, TNF-␣, and CSE. ChAT, M 1 , and M 3 expression and ERK1/2 and NFB activation were increased, whereas M 2 was reduced, in COPD and smoker subjects compared with controls. IL-1␤ increased the ChAT and M 3 , TNF-␣ down-regulated M 2 , and CSE increased ChAT and M 3 expression while downregulating the expression of M 2 in HFL-1 cells. ACh stimulation increased fibroblast proliferation in patients with COPD, control smokers, and controls, with higher effect in control smokers and patients with COPD and increased HFL-1 proliferation only in CSE-treated cells. The binding of ACh was higher in patients with COPD and in control smokers than in controls and in CSE-treated than in IL-1␤-and TNF-␣-stimulated HFL-1 cells. Tiotropium (Spiriva; [1␣,2␤,4␤,5␣,7␤-7-hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatrcyclo[3.3. [(E)-3-(4-methylphenylsulfonyl)-2-propenetrile, C 10 H 9 NO 2 C], down-regulated the ACh-induced fibroblast proliferation, promoting the MRs and ERK1/2 and NFB pathways involvement in this phenomenon. These results suggest that cigarette smoke might alter the expression of ChAT and MRs, promoting airway remodeling in COPD and that anticholinergic drugs, including tiotropium, might prevent these events.An overpresence of fibroblasts has been observed in chronic airway diseases and several factors, released by both parenchymal and inflammatory cells, can contribute to this event promoting fibroblast proliferation (Jeffery, 1998 ABBREVIATIONS: M 1 , muscarinic M 1 receptor; M 2 , muscarinic M 2 receptor; M 3 , muscarinic M 3 receptor; MR, muscarinic M 1 , M 2 , and M 3 receptor; MAPK, mitogen-activated protein kinase; ACh, acetylcholine; ChAT, choline acetyltransferase; COPD, chronic obstructive pulmonary disease; IL, interleukin; TNF, tumor necrosis factor; CS, cigarette smoke; ERK, extracellular signal-regulated kinase; NF, nuclear factor; CSE, cigarette smoke extract; C, asymptomatic nonsmoking subject(s) with normal lung function; FBS, fetal bovine serum; PAGE, polyacrylamide gel electrophoresis; FITC, fluorescein isothiocyanate; ELISA, enzyme-linked immunosorbent assay; pNFB, phosphorylated NFB; tNFB, total NFB; tiotropium, Spiriva, [1␣,2␤,4␤,5␣,7␤-7-hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatrcyclo[3.3. O; 4-DAMP, 4-diphenylacetoxy-N...

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“…Significantly higher serum cytokine and salivary levels of messenger RNA (mRNA) for tumor necrosis factor ␣ (TNF␣), interleukin-6 (IL-6), IL-10, interferon-␥ (IFN␥), and lower salivary gland expression of transforming growth factor ␤1 (TGF␤1) have been found in SS patients than in healthy control subjects (2)(3)(4). Additionally, there is a strong rationale for the intervention of each of these cytokines in the pathogenesis of SS (5)(6)(7)(8)(9).…”

mentioning

confidence: 99%

Association of transforming growth factor β1 and tumor necrosis factor α polymorphisms with anti‐SSB/La antibody secretion in patients with primary Sjögren's syndrome

Gottenberg¹,

Busson²,

Loiseau³

et al. 2004

Arthritis & Rheumatism

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Objective. To determine whether cytokine gene polymorphisms of interferon-␥ (IFN␥), interleukin-6 (IL-6), IL-10, tumor necrosis factor ␣ (TNF␣), and transforming growth factor ␤1 (TGF␤1) predispose subjects to the development of primary Sjögren's syndrome (SS).Methods. Single-base-exchange cytokine gene polymorphisms were analyzed in 129 French patients with primary SS who fulfilled the American-European Consensus Group criteria, as well as in 96 unrelated healthy subjects.Results. The frequency of the TNF-308A (TNF2) allele was significantly higher in the SS patients (26% versus 11%). This TNF2 association was restricted to patients with anti-SSB (37% versus 11% in controls). Stratification did not reveal an independent effect of TNF2 and HLA-DRB1*03 on disease or on anti-SSB antibody secretion. The frequency of allele C at codon 10 of TGF␤1 was strongly increased in the subgroup of patients with anti-SSB; this allele acted synergistically with DRB1*03 to predispose patients to the secretion of anti-SSB. The IL-10 GCC haplotype carrier rate was significantly higher in SS patients than in controls (67% versus 48%), but the IL-10 allele and genotype frequencies were not significantly different. No association was found between IL-6 or IFN␥ polymorphisms and primary SS.Conclusion. TNF2 was associated with anti-SSB antibody secretion, although this association was not independent of the association with DRB1*03. Allele C at codon 10 of TGF␤1 was found to act synergistically with DRB1*03 in predisposing patients to the secretion of anti-SSB. These results therefore suggest that most of the known genetic predisposition to primary SS might concern the pattern of autoantibody diversification.

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Synergy between Tumor Necrosis Factor α and Interleukin 1β in Inducing Transcriptional Down-regulation of Muscarinic M2 Receptor Gene Expression

Cited by 59 publications

References 46 publications

IL-1 Receptors Mediate Persistent, but Not Acute, Airway Hyperreactivity to Ozone in Guinea Pigs

IL-1 Receptors Mediate Persistent, but Not Acute, Airway Hyperreactivity to Ozone in Guinea Pigs

Smoke, Choline Acetyltransferase, Muscarinic Receptors, and Fibroblast Proliferation in Chronic Obstructive Pulmonary Disease

Association of transforming growth factor β1 and tumor necrosis factor α polymorphisms with anti‐SSB/La antibody secretion in patients with primary Sjögren's syndrome

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