title: Cross-talk between interleukin-6 and transforming growth factor-beta3 regulates extracellular matrix production by human fibroblasts from subjects with non-syndromic cleft lip and palate.
abstract: BACKGROUND
  Transforming growth factor-beta (TGF-beta) interference with interleukin 6 (IL-6) activity and the role of the latter in early human embryonic development prompted us to examine the effects IL-6 on matrix synthesis and the effects of TGF-beta3 on IL-6 expression human cleft lip and palate (CLP) fibroblasts.
  
  
  METHODS
  Collagen and glycosaminoglycan (GAG) synthesis were determined by radiolabeled precursors and biglycan expression by Northern blotting before and after adding IL-6. The effects of TGF-beta3 on IL-6 production were assayed by evaluating IL-6 transcript by Northern blotting and IL-6 protein secretion by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The results showed that IL-6 elicited an inhibitory effect on collagen and GAG levels in CLP fibroblasts by lowering hyaluronan and dermatan sulfate secretion. IL-6 up-regulated biglycan expression, but less strongly than TGF-beta3. TGF-beta3 significantly down-regulated IL-6 transcript and secretion in CLP fibroblasts.
  
  
  CONCLUSIONS
  These data suggest the increase in matrix components that characterize the CLP fibroblast phenotype might be due to a concerted TGF-beta3-IL-6 action. We hypothesize changes in cross-talk between TGF-beta3 and IL-6 signal transduction pathways are involved in the induction of cleft palate.
authors.affiliation: Section of Histology and Embryology, Faculty of Medicine, University of Perugia, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Baroni
authors.forename: Paolo
authors.initials: P
authors.lastname: Carinci
authors.forename: Catia
authors.initials: C
authors.lastname: Bellucci
authors.forename: Cinzia
authors.initials: C
authors.lastname: Lilli
authors.forename: Ennio
authors.initials: E
authors.lastname: Becchetti
authors.forename: Francesco
authors.initials: F
authors.lastname: Carinci
authors.forename: Giordano
authors.initials: G
authors.lastname: Stabellini
authors.forename: Furio
authors.initials: F
authors.lastname: Pezzetti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Caramelli
authors.forename: Mauro
authors.initials: M
authors.lastname: Tognon
authors.forename: Maria
authors.initials: M
authors.lastname: Bodo
mesh_terms: D000704:Analysis of Variance; D002478:Cells, Cultured; D002675:Child, Preschool; D002971:Cleft Lip / Q000378:metabolism; D002972:Cleft Palate / Q000209:etiology / Q000378:metabolism*; D003094:Collagen / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D011509:Proteoglycans / Q000096:biosynthesis; D020239:Receptor Cross-Talk; D015398:Signal Transduction / Q000187:drug effects; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D053782:Transforming Growth Factor beta3
chemical_list: D006025:Glycosaminoglycans; D015850:Interleukin-6; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D003094:Collagen