title: Mechanism of inhibitory effect of prednisolone on RhoA upregulation in human bronchial smooth muscle cells.
abstract: RhoA plays an important role in Ca(2+) sensitization of bronchial smooth muscle in antigen-induced airway hyperresponsiveness (AHR). Glucocorticoids are now the most effective anti-inflammatory treatment for asthma, and inhaled corticosteroids are the most effective long-term control therapy for persistent asthma. To determine the mechanism of the inhibitory action of glucocorticoids on AHR in allergic bronchial asthma, that of prednisolone on RhoA upregulation was investigated using cultured human bronchial smooth muscle cells (hBSMCs). The upregulation of RhoA induced by interleukin (IL)-13 and tumor necrosis factor (TNF)-alpha, major mediators for development of AHR, was observed in hBSMCs. Prednisolone partly inhibited the IL-13-induced RhoA upregulation and RhoA promoter activity, although prednisolone had no effects on the activations of signal transducers and activators of transcription (STAT)6 and nuclear factor (NF)-kappaB. Increased expression and promoter activity of RhoA induced by TNF-alpha was completely inhibited by prednisolone, although the activation of NF-kappaB failed to be inhibited by prednisolone in hBSMCs. These findings suggest that prednisolone might inhibit NF-kappaB-induced transcription via interaction between glucocorticoid receptor (GR), resulting in an inhibition of RhoA upregulation induced by IL-13 and TNF-alpha.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Hoshi University, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Goto
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Chiba
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sakai
authors.forename: Miwa
authors.initials: M
authors.lastname: Misawa
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001249:Asthma / Q000235:genetics / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D011239:Prednisolone / Q000494:pharmacology* / Q000627:therapeutic use; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D018793:Interleukin-13; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D011239:Prednisolone; D020742:rhoA GTP-Binding Protein