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The cytokine IL-6 acts via a specific receptor complex that consists of the membrane-bound IL-6 receptor (mIL-6R) or the soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (gp130). In this study, we investigated the role of IL-6R components in asthma. We observed increased levels of sIL-6R in the airways of patients with allergic asthma as compared to(More)
In human embryonic lung fibroblasts, transforming growth factor-beta 1 (TGF-beta 1) induced a time-dependent down-regulation of M2 muscarinic receptor binding sites as measured with the nonselective hydrophilic ligand [3H]N-methylscopolamine (NMS). This down-regulation was slow, with 58% loss of all receptors after 24 hr of treatment. The affinity of(More)
Bradykinin (BK) is a peptide mediator generated at sites of inflammation and its effects are mediated through constitutively expressed B(2) receptor or through induction of B(1) receptors. We examined the role of these receptors in bronchial hyperresponsiveness (BHR). Brown-Norway rats sensitized with ovalbumin (OA) and Al(OH)(3) intraperitoneally, were(More)
Bombesin (Bn) and related agonists produce a potent contractile response in guinea pig peripheral airways in vitro, with the following relative potencies: bombesin > gastrin-releasing peptide (GRP) > neuromedin C >> neuromedin B. Specific GRP-preferring receptor antagonists, namely [D-Phe6]Bn-(6-13)methyl ester and [D-Phe6,Cpa14,psi 13-14]Bn(6-14)-NH2,(More)
The muscarinic receptors present in the guinea pig tracheobronchial tree were characterized using ligand-binding studies and functional approaches. The binding constants of four selective antagonists, pirenzepine,[11-([2-[(diethylamino) methyl]-1-piperidinyl]acetyl)-5,11-dihydro-6H-pyrido(2,3) (1,4) benzodiazepine-6-on] (AF-DX 116), methoctramine, and(More)
We examined the binding of [3H]bradykinin ([3H]BK) to the guinea-pig lung which was saturable. Scatchard analysis indicated the existence of two binding sites, one with a high affinity (KD = 15 pM) and one with a low one (KD = 570 pM) with maximum number of binding sites of 12 and 45 fmol/mg protein, respectively. Kinetic studies confirmed the presence of(More)
1. The molecular mechanisms involved in the regulation of muscarinic receptor gene expression are poorly understood. We have investigated the effect of homologous stimulation on the regulation of M2 muscarinic receptor protein and gene in human embryonic lung fibroblasts (HEL 299 cells). 2. Saturation studies performed with the non-selective hydrophilic(More)
We investigated the effect of the glucocorticoid methylprednisolone on the modulation of the expression of the bradykinin B2 receptors in cultured, guinea-pig, tracheal, smooth muscle cells. These receptors are implicated in the pathogenesis of human asthma. Untreated cells expressed a single population of binding sites for [3H]bradykinin with a(More)
We postulated that the seleno-organic compound ebselen would attenuate neutrophil recruitment and activation after aerosolized challenge with endotoxin (LPS) through its effect as an antioxidant and inhibitor of gene activation. Rats were given ebselen (1-100 mg/kg i.p.) followed by aerosolized LPS exposure (0.3 mg/ml for 30 min). Airway inflammatory(More)
Excessive local production of nitric oxide (NO) has been suggested to play a role in rodent models of airway inflammation and in pulmonary diseases such as asthma. However, even given the plethora of data available including gene expression data, pharmacological data, and gene deletion studies in animal models, it is still not clear which nitric-oxide(More)