Procaterol inhibits IL-1β- and TNF-α-mediated epithelial cell eosinophil chemotactic activity

Abstract

Theophylline inhibits eosinophilic infiltration into the bronchial wall. It is unknown whether this is mediated by a cyclic adenosine monophosphate (c-AMP) -dependent reduction in eosinophil chemotactic activity (ECA) from bronchial epithelial cells (BEC). Therefore the effect of a b 2 -agonist, procaterol and theophylline on the release of ECA from a BEC line, BEAS-2B was evaluated in response to interleukin (IL)-1b and tumour necrosis factor-a (TNF-a).ECA was assessed using a blind-well chemotactic chamber, and the release and gene expression of cytokines were evaluated by means of enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction.IL-1b and TNF-a stimulated the release of ECA from BEAS-2B cells in a dose-and time-dependent manner. Procaterol and theophylline directly inhibited eosinophil migration to IL-1b and TNF-a-conditioned medium. The pretreatment of BEAS-2B cells with the same concentrations of procaterol inhibited the release of ECA in a dosedependent fashion. Anti-IL-8, anti-regulated on activation, normal T-cell expressed and secreted (RANTES), and anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) inhibited ECA. Procaterol inhibited the release of RANTES, GM-CSF and IL-8 in a dose-dependent fashion. The effect of theophylline was less potent. Procaterol augmented cAMP levels in BEAS-2B cells in a time-and dose-dependent manner. The expression of IL-8, RANTES, and GM-CSF messenger ribonucleic acid was not inhibited by procaterol and theophylline.These data indicate that procaterol and theophylline may directly inhibit eosinophil migration and that procaterol may further inhibit the release of eosinophil chemotactic activity from BEAS-2B cells via a cyclic adenosine monophosphate-dependent mechanism. This warrants further studies on the involvement of bronchial epithelial cells in the anti-inflammatory effects of procaterol and theophylline in patients with asthma. Eur Respir J 1999; 14: 767±775.

Association Between C Reactive Protein and Asthma

“…Both TNF-Alfa and IL-1 affect numerous processes that may be important in asthma. These cytokines increase adhesion of eosinophils to epithelial cells [42], cause release of eotoxin, a potent chemotactic agents for eosinophils from lung fibroblast [43] and epithelial cells [44,45], cause release of IL-9 from eosinophils [46], up regulate IL-8 production by alveolar macrophages [47] increase IL-8 mRNA of bronchial epithelial cells [48], damage bronchial epithelial cells [49], activate endothelial cells [50], increase cyclooxygenase -2 activity [51] and cause bronchoconstriction [52].…”

β2‐Adrenergic receptor regulation of human neutrophil function is sexually dimorphic

“…Neutrophil b 2 -adrenoceptors are sexually dimorphicIL-1b or TNF-a (Koyama et al, 1999). This effect of a badrenergic receptor agonist to attenuate neutrophil recruitment by strong chemoattractants is an important aspect of the anti-inflammatory properties of b 2 -adrenergic receptors.…”

Proteasome inhibitors modulate chemokine production in lung epithelial and monocytic cells

“…In lung epithelial cells the production of the chemokine IL-8 is induced by alveolar macrophage-derived proinflammatory cytokines IL-1a/b, TNF-a [7], bacterial cell wall products [8], and viruses [9,10]. The stimulus-specific inducible IL-8 production is regulated primarily at the level of gene transcription.…”