title: Th17 cytokines induce pro-fibrotic cytokines release from human eosinophils.
abstract: BACKGROUND
  Subepithelial fibrosis is one of the most critical structural changes affecting bronchial airway function during asthma. Eosinophils have been shown to contribute to the production of pro-fibrotic cytokines, TGF-β and IL-11, however, the mechanism regulating this process is not fully understood.
  
  
  OBJECTIVE
  In this report, we investigated whether cytokines associated with inflammation during asthma may induce eosinophils to produce pro-fibrotic cytokines.
  
  
  METHODS
  Eosinophils were isolated from peripheral blood of 10 asthmatics and 10 normal control subjects. Eosinophils were stimulated with Th1, Th2 and Th17 cytokines and the production of TGF-β and IL-11 was determined using real time PCR and ELISA assays.
  
  
  RESULTS
  The basal expression levels of eosinophil derived TGF-β and IL-11 cytokines were comparable between asthmatic and healthy individuals. Stimulating eosinophils with Th1 and Th2 cytokines did not induce expression of pro-fibrotic cytokines. However, stimulating eosinophils with Th17 cytokines resulted in the enhancement of TGF-β and IL-11 expression in asthmatic but not healthy individuals. This effect of IL-17 on eosinophils was dependent on p38 MAPK activation as inhibiting the phosphorylation of p38 MAPK, but not other kinases, inhibited IL-17 induced pro-fibrotic cytokine release.
  
  
  CONCLUSIONS
  Th17 cytokines might contribute to airway fibrosis during asthma by enhancing production of eosinophil derived pro-fibrotic cytokines. Preventing the release of pro-fibrotic cytokines by blocking the effect of Th17 cytokines on eosinophils may prove to be beneficial in controlling fibrosis for disorders with IL-17 driven inflammation such as allergic and autoimmune diseases.
authors.affiliation: Asthma Research Chair and Prince Naif Center for Immunology Research, Department of Paediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Muhsen
authors.forename: Severine
authors.initials: S
authors.lastname: Letuve
authors.forename: Alejandro
authors.initials: A
authors.lastname: Vazquez-Tello
authors.forename: Mary Angeline
authors.initials: MA
authors.lastname: Pureza
authors.forename: Hamdan
authors.initials: H
authors.lastname: Al-Jahdali
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Bahammam
authors.forename: Qutayba
authors.initials: Q
authors.lastname: Hamid
authors.forename: Rabih
authors.initials: R
authors.lastname: Halwani
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D001980:Bronchi / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000276:immunology* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D006801:Humans; D007249:Inflammation / Q000276:immunology; D017370:Interleukin-11 / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology*; D008297:Male; D016133:Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016207:Cytokines; D017370:Interleukin-11; D020381:Interleukin-17; D016212:Transforming Growth Factor beta