title: Interleukin-23 deficiency leads to impaired wound healing and adverse prognosis after myocardial infarction.
abstract: BACKGROUND
  CD4+ cells are implicated in the healing process after myocardial infarction (MI). We sought to investigate the role of interleukin-23 (IL-23) deficiency, a cytokine important in differentiation of CD4+ cells, in scar formation of the ischemic heart.
  
  
  RESULTS
  MI was performed in wild-type and IL23p19-/- mice. Thirty-day mortality, hemodynamic function 4 days after MI and myocardial inflammation, and remodeling 4 and 30 days after MI were examined. Differentiation of fibroblasts from infarcted and noninfarcted hearts into myofibroblasts was examined under basal conditions and after stimulation with interferon-γ, IL-17α and IL-23. Interleukin-23p19-/- mice showed higher expression of proinflammatory cytokines and immune cell infiltration in the scar early after MI compared with wild-type mice. A stronger interferon-γ/Th1 reaction seemed to be responsible for the increased inflammation under IL-23 deficiency. Expression of α-smooth muscle actin (α-SMA), collagen I and III was significantly higher in the heart tissue and isolated cardiac fibroblasts 4 days after MI in the wild-type mice. Interleukin-23p19-/- mice showed impaired healing compared with wild-type mice, as seen by significantly higher mortality because of ventricular rupture (40% higher after 30 days) and stronger left ventricular dilation early after MI. Stimulation of cardiac fibroblasts with interferon-γ, the main Th1 cytokine, but not with IL-23 or IL-17α, led to a significant downregulation of α-smooth muscle actin, collagen I and III and decreased migration and differentiation to myofibroblasts.
  
  
  CONCLUSIONS
  IL-23 deficiency leads to increased myocardial inflammation and decreased cardiac fibroblast activation, associated with impaired scar formation and adverse remodeling after MI.
authors.affiliation: Department of Cardiology and Pneumology, Campus Benjamin Franklin.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Savvatis
authors.forename: Kathleen
authors.initials: K
authors.lastname: Pappritz
authors.forename: Peter Moritz
authors.initials: PM
authors.lastname: Becher
authors.forename: Diana
authors.initials: D
authors.lastname: Lindner
authors.forename: Christin
authors.initials: C
authors.lastname: Zietsch
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Dirk
authors.initials: D
authors.lastname: Westermann
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Carsten
authors.initials: C
authors.lastname: Tschöpe
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002921:Cicatrix / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D007371:Interferon-gamma / Q000494:pharmacology; D020381:Interleukin-17 / Q000494:pharmacology; D053759:Interleukin-23 / Q000172:deficiency* / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000401:mortality / Q000503:physiopathology*; D011379:Prognosis; D014945:Wound Healing / Q000502:physiology*
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D053759:Interleukin-23; D007371:Interferon-gamma
keywords: fibroblasts; interleukin-23; left ventricular remodeling; myocardial infarction