title: Interleukin-6 receptor superantagonist Sant7 inhibits TGF-beta-induced proliferation of human lung fibroblasts.
abstract: OBJECTIVE
  Both interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta) are crucially involved in fibrotic events that characterize interstitial lung diseases (ILD). Therefore, the aim of this study was to investigate in primary cultures of normal and fibrotic human lung fibroblasts (HLF), exposed to either IL-6 or TGF-beta1, the effects on phosphorylation of mitogen-activated protein kinases (MAPK) and cell growth of IL-6 signalling inhibition, performed by the IL-6 receptor superantagonist Sant7.
  
  
  METHODS
  MAPK phosphorylation was detected by Western blotting, HLF viability and proliferation were evaluated using the trypan blue staining and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, respectively.
  
  
  RESULTS
  Sant7, at a concentration of 1 microg/mL, was capable of significantly inhibiting HLF proliferation and MAPK phosphorylation induced by cell exposure to IL-6 (100 ng/mL) or TGF-beta1 (10 ng/mL), whose actions were more evident in fibrotic cells.
  
  
  CONCLUSIONS
  These findings suggest that, in HLFs derived from patients with ILDs, the proliferative mechanisms activated by TGF-beta1 are at least in part mediated by an increased release of IL-6, leading to phosphorylation-dependent MAPK activation. Such preliminary findings may thus open new therapeutic perspectives for fibrogenic ILDs, based on inhibition of signal transduction pathways stimulated by the IL-6 receptor.
authors.affiliation: Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Gallelli
authors.forename: D
authors.initials: D
authors.lastname: Falcone
authors.forename: G
authors.initials: G
authors.lastname: Pelaia
authors.forename: T
authors.initials: T
authors.lastname: Renda
authors.forename: R
authors.initials: R
authors.lastname: Terracciano
authors.forename: N
authors.initials: N
authors.lastname: Malara
authors.forename: A
authors.initials: A
authors.lastname: Vatrella
authors.forename: A
authors.initials: A
authors.lastname: Sanduzzi
authors.forename: B
authors.initials: B
authors.lastname: D'Agostino
authors.forename: F
authors.initials: F
authors.lastname: Rossi
authors.forename: C
authors.initials: C
authors.lastname: Vancheri
authors.forename: R
authors.initials: R
authors.lastname: Maselli
authors.forename: S A
authors.initials: SA
authors.lastname: Marsico
authors.forename: R
authors.initials: R
authors.lastname: Savino
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D015850:Interleukin-6 / Q000031:analogs & derivatives* / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008168:Lung / Q000166:cytology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D019947:Receptors, Interleukin-6; C432252:SANT-7; D053773:Transforming Growth Factor beta1; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases