Tumor necrosis factor-alpha inhibits collagen synthesis in human and rat granulation tissue fibroblasts.
The purpose of the study was to examine the effects of tumor necrosis factor-alpha (TNF-alpha) on collagen gene expression in rat and human granulation tissue fibroblast cultures. The cells were exposed to 0.1, 1, 10, or 100 ng/ml of TNF-alpha, and the rate of collagen synthesis was measured as synthesis of protein-bound 3H-hydroxy-proline. Total cellular RNA was isolated from fibroblasts, and measurements of specific cellular RNAs from fibroblasts were performed by Northern blot hybridizations using 32P-labeled cDNA probes. In cultures of rat granulation tissue fibroblasts TNF-alpha decreased 3H-hydroxyproline production to about 75% of that in controls and it also decreased pro alpha 1(I) and pro alpha 1(III) collagen mRNA levels, maximally to 33% and 23% of the control levels, respectively. In cultures of human granulation tissue fibroblasts a similar inhibiting effect in the production of collagen was seen. TNF-alpha decreased the production of 3H-hydroxyproline to 56% of the control value with a dose of 100 ng/ml also having an inhibiting effect on pro alpha 1(I) collagen mRNA levels of up to 43% of the control level. However, no effect was seen on pro alpha 1(III) collagen mRNA levels.
Rapala
K T
KT
Department of Surgery, University of Turku, Finland.
Vähä-Kreula
M O
MO
Heino
J J
JJ
Vuorio
E I
EI
Laato
M K
MK
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006097:Granulation Tissue / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen