title: N-acetylcysteine and azithromycin affect the innate immune response in cystic fibrosis bronchial epithelial cells in vitro.
abstract: OBJECTIVE
  We have previously reported that N-acetylcysteine (NAC), ambroxol and azithromycin (AZM) (partially) correct the chloride efflux dysfunction in cystic fibrosis bronchial epithelial (CFBE) cells with the ΔF508 homozygous mutation in vitro.
  
  
  METHODS
  In the present paper, we further investigated possible immunomodulatory effects of these drugs on the regulation of the innate immune system by studying the expression of the cytosolic NOD-like receptors NLRC1 and NLRC2, and interleukin (IL)-6 production in CFBE cells.
  
  
  RESULTS
  Under basal conditions, PCR and Western Blot data indicate that the NLRC2 receptor has a reduced expression in CF cells as compared to non-CF (16HBE) cells, but that the NLRC1 expression is the same in both cell lines. AZM significantly upregulated NLRC1 and NLRC2 while NAC upregulated only NLRC2 receptor expression in CF cells. Reduced basal IL-6 production was found in CF cells as compared to non-CF cells. MDP (an NLRC2 agonist), NAC and AZM, but not Tri-DAP (an NLRC1 agonist), increased IL-6 production in CF cells, indicating that in CF cells IL-6 upregulation is independent of NLRC1, but involves the activation of NLRC2.
  
  
  CONCLUSIONS
  Overall, the results indicate that NAC and AZM not only can correct the chloride efflux dysfunction but also have a weakly strengthening effect on the innate immune system.
authors: 1School of Health and Medical Sciences, Örebro University , Örebro , Sweden.
authors: Shahida
authors: S
authors: Hussain
authors: Georgia
authors: G
authors: Varelogianni
authors: Eva
authors: E
authors: Särndahl
authors: Godfried M
authors: GM
authors: Roomans
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D003550:Cystic Fibrosis / Q000276:immunology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D053474:Nod1 Signaling Adaptor Protein / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D015850:Interleukin-6; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D017963:Azithromycin; D000111:Acetylcysteine
keywords: Cystic fibrosis; NOD-like receptors; chloride efflux activators