Mono- and cocultures of bronchial and alveolar epithelial cells respond differently to proinflammatory stimuli and their modulation by salbutamol and budesonide

Mehra Haghi, Marius Hittinger, Qingxiang Zeng, Brian Oliver, Daniela Traini, Paul M. Young, Hanno Huwer, Nicole Schneider-Daum*, Claus Michael Lehr

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2625-2632
Number of pages8
JournalMolecular Pharmaceutics
Volume12
Issue number8
DOIs
Publication statusPublished - 3 Aug 2015
Externally publishedYes

Keywords

  • airway smooth muscle cells
  • alveolar macrophages
  • cytokine
  • epithelial transport
  • inflammation

Fingerprint

Dive into the research topics of 'Mono- and cocultures of bronchial and alveolar epithelial cells respond differently to proinflammatory stimuli and their modulation by salbutamol and budesonide'. Together they form a unique fingerprint.

Cite this