title: Oncostatin M causes eotaxin-1 release from airway smooth muscle: synergy with IL-4 and IL-13.
abstract: BACKGROUND
  Eotaxin is implicated in asthmatic eosinophilia. Oncostatin M (OSM) causes eotaxin release from fibroblasts.
  
  
  OBJECTIVE
  We sought to examine the effects and mechanism of action of OSM and other IL-6 family cytokines on eotaxin release from human airway smooth muscle cells.
  
  
  METHODS
  Eotaxin 1 release was measured by means of ELISA. Western blotting was used to examine mitogen-activated protein kinase and signal transducer and activator of transcription 3 (STAT-3) phosphorylation. Eotaxin promoter activity was analyzed in cells transfected with wild-type STAT-3, a mutant form of STAT-3 that cannot be phosphorylated, and a constitutively active form of STAT-3. The mRNA and protein expression of IL-4R alpha, the signaling receptor for IL-4 and IL-13, was evaluated by means of real-time PCR and flow cytometry, respectively.
  
  
  RESULTS
  OSM increased eotaxin 1 release and augmented IL-4- or IL-13-induced eotaxin release, whereas other IL-6 family cytokines did not. OSM caused a greater increase in STAT-3 phosphorylation and STAT-3-mediated gene transcription than other IL-6 family cytokines. OSM increased eotaxin promoter activity and augmented IL-13- and IL-4-induced increases in promoter activity. The constitutively active form of STAT-3 increased eotaxin promoter activity, whereas the mutant form of STAT-3 that cannot be phosphorylated significantly reduced eotaxin promoter activity induced by OSM or IL-4 plus OSM. OSM increased IL-4R alpha mRNA and protein levels.
  
  
  CONCLUSIONS
  OSM induces eotaxin 1 expression in human airway smooth muscle cells by a mechanism involving STAT-3. OSM synergizes with IL-13 and IL-4 to increase eotaxin 1 expression, possibly as a result of effects on IL-4R alpha expression.
authors.affiliation: Physiology Program, Harvard School of Public Health, Boston, Mass 02115, USA.
authors.forename: Débora S
authors.initials: DS
authors.lastname: Faffe
authors.forename: Lesley
authors.initials: L
authors.lastname: Flynt
authors.forename: Matthew
authors.initials: M
authors.lastname: Mellema
authors.forename: Paul E
authors.initials: PE
authors.lastname: Moore
authors.forename: Eric S
authors.initials: ES
authors.lastname: Silverman
authors.forename: Venkat
authors.initials: V
authors.lastname: Subramaniam
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Jones
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Mizgerd
authors.forename: Timothy
authors.initials: T
authors.lastname: Whitehead
authors.forename: Amy
authors.initials: A
authors.lastname: Imrich
authors.forename: Reynold A
authors.initials: RA
authors.lastname: Panettieri
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Shore
mesh_terms: D015153:Blotting, Western; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000276:immunology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D019948:Receptors, Interleukin-4 / Q000187:drug effects / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D018793:Interleukin-13; C508351:OSM protein, human; D010455:Peptides; D012333:RNA, Messenger; D019948:Receptors, Interleukin-4; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D053683:Oncostatin M; D015847:Interleukin-4; D020928:Mitogen-Activated Protein Kinases