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.
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.
Baroni
Tiziano
T
Section of Histology and Embryology, Faculty of Medicine, University of Perugia, Italy.
Carinci
Paolo
P
Bellucci
Catia
C
Lilli
Cinzia
C
Becchetti
Ennio
E
Carinci
Francesco
F
Stabellini
Giordano
G
Pezzetti
Furio
F
Caramelli
Elisabetta
E
Tognon
Mauro
M
Bodo
Maria
M
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
D006025:Glycosaminoglycans; D015850:Interleukin-6; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D003094:Collagen