title: Mono- and Cocultures of Bronchial and Alveolar Epithelial Cells Respond Differently to Proinflammatory Stimuli and Their Modulation by Salbutamol and Budesonide.
abstract: The aim of this study was to investigate the changes in transport and effectiveness of salbutamol sulfate (SAL) and budesonide (BD) following stimulation with transforming growth factor-β (TGF-β) in mono- and coculture models of bronchial and alveolar epithelium. Primary bronchial and alveolar epithelial cells, grown at air interface on filters, either as monocultures or in coculture with airway smooth muscle cells or alveolar macrophages, respectively, were stimulated with TGF-β. The biological response was modulated by depositing aerosolized SAL and BD on bronchial and alveolar models, respectively. Barrier integrity, permeability to fluorescein-Na, transport of the deposited drug, and the pharmacological response to SAL (cAMP and IL-8 levels) or BD (IL-6 and -8 levels) were measured. While stimulation with TGF-β did not have any significant effect on the transepithelial electrical resistance and permeability to fluorescein-Na in mono- and coculture models, transport of SAL and BD were affected in cultures from some of the patients (6 out of 12 for bronchial and 2 out of 4 for alveolar cells). The bronchial coculture showed a better responsiveness to SAL in terms of cAMP release than the monoculture. In contrast, the difference between alveolar mono- and cocultures to TGF-β mediated interleukin release and its modulation by BD was less pronounced. Our data point to intrinsic differences in the transport of, and responsiveness to, SAL and BD when epithelial cell cultures originate from different patients. Moreover, if the biological responses (e.g., IL-8, cAMP) involve communication between different cell types, coculture models are more relevant to measure such effects than monocultures.
authors.affiliation: †Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), 66123 Saarbrücken, Germany.|‡School of Pharmacy, Graduate School of Health, The University of Technology Sydney, New South Wales 2007, Australia.|§Woolcock Institute for Medical Research and Discipline of Pharmacology, Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Mehra
authors.initials: M
authors.lastname: Haghi
authors.affiliation: †Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), 66123 Saarbrücken, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Hittinger
authors.affiliation: ∥Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Qingxiang
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: §Woolcock Institute for Medical Research and Discipline of Pharmacology, Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Brian
authors.initials: B
authors.lastname: Oliver
authors.affiliation: §Woolcock Institute for Medical Research and Discipline of Pharmacology, Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Daniela
authors.initials: D
authors.lastname: Traini
authors.affiliation: §Woolcock Institute for Medical Research and Discipline of Pharmacology, Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Young
authors.affiliation: #Department of Cardiothoracic Surgery, Voelklingen Heart Centre, 66333 Völklingen, Germany.
authors.forename: Hanno
authors.initials: H
authors.lastname: Huwer
authors.affiliation: †Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), 66123 Saarbrücken, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schneider-Daum
authors.affiliation: †Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), 66123 Saarbrücken, Germany.|°Biopharmaceutics and Pharmaceutical Technology, Faculty of of Pharmacy, Saarland University, 66123 Saarbrücken, Germany.
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D000420:Albuterol / Q000493:pharmacokinetics / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D001993:Bronchodilator Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D019819:Budesonide / Q000493:pharmacokinetics / Q000494:pharmacology*; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000493:pharmacokinetics / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D001993:Bronchodilator Agents; D018836:Inflammation Mediators; D016212:Transforming Growth Factor beta; D019819:Budesonide; D000420:Albuterol
keywords: airway smooth muscle cells; alveolar macrophages; cytokine; epithelial transport; inflammation