title: Th-17 regulatory cytokines inhibit corticosteroid induced airway structural cells apoptosis.
abstract: BACKGROUND
  Although corticosteroid is a powerful anti-inflammatory drug that is used widely to control asthma, still severe asthmatics can develop steroid resistance. Airway fibroblasts are quite resistant to steroids during Idiopathic pulmonary fibrosis (IPF) and fibrosis in asthmatic lungs is not always controlled. Th-17 regulatory cytokine which are elevated in lung tissues of asthmatics were shown to enhance the survival of various types of cells. STAT factors are central to this anti-apoptotic function. However, it is not yet clear whether these cytokines contribute to steroid hypo-responsiveness in asthma. Therefore, in this study, we investigated the ability of Th-17 regulatory cytokines, specifically IL-21, IL22 and IL23, to protect structural airway cells against dexamethasone-induced apoptosis.
  
  
  METHODS
  Primary human fibroblasts, ASM cells, and lung endothelial cells line were treated with IL-21, IL-22, and IL-23 cytokines before incubation with dexamethasone and the level of apoptosis was determined by measuring cellular Annexin-V using Flow cytometry.
  
  
  RESULTS
  Our data indicated that treatment with Th-17 regulatory cytokines was effective in inhibiting induced apoptosis for both fibroblasts and endothelial cells but not ASM cells. STAT3 phosphorylation levels were also upregulated in fibroblasts and endothelial upon treatment with these cytokines. Interestingly, inhibiting STAT3 phosphorylation abrogated IL-21, IL-22, and IL-23 anti-apoptotic effect on fibroblasts and endothelial cells.
  
  
  CONCLUSIONS
  This data suggest that Th-17 regulatory cytokines may play a critical role in regulating the survival of fibroblasts during asthma, IPF as well as other chronic lung inflammatory diseases leading to enhanced fibrosis. Accordingly, findings of this paper may pave the way for more extensive research on the role of these regulatory cytokines in fibrosis development in various chronic inflammatory diseases.
authors.affiliation: Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, King Saud University, P. O. Box 2925, Postal Code 11461, Riyadh, Saudi Arabia. rhalwani@ksu.edu.sa.
authors.forename: Rabih
authors.initials: R
authors.lastname: Halwani
authors.affiliation: Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, King Saud University, P. O. Box 2925, Postal Code 11461, Riyadh, Saudi Arabia.|Prince Naif Health Research Center, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Asma
authors.initials: A
authors.lastname: Sultana
authors.affiliation: Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, King Saud University, P. O. Box 2925, Postal Code 11461, Riyadh, Saudi Arabia.
authors.forename: Roua
authors.initials: R
authors.lastname: Al-Kufaidy
authors.affiliation: Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, King Saud University, P. O. Box 2925, Postal Code 11461, Riyadh, Saudi Arabia.
authors.forename: Amer
authors.initials: A
authors.lastname: Jamhawi
authors.affiliation: Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, King Saud University, P. O. Box 2925, Postal Code 11461, Riyadh, Saudi Arabia.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Vazquez-Tello
authors.affiliation: Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, King Saud University, P. O. Box 2925, Postal Code 11461, Riyadh, Saudi Arabia.
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Muhsen
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D003907:Dexamethasone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D007155:Immunologic Factors / Q000276:immunology; D008168:Lung / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007155:Immunologic Factors; D003907:Dexamethasone