Tumour necrosis factor-alpha selectivity modulates expression of collagen genes in rat granulation tissue.
OBJECTIVE
To study the effects of tumour necrosis factor-alpha (TNF-alpha) on granulation tissue in rats.


METHODS
Animal experiment.


METHODS
University Hospital, Finland.


METHODS
48 rats in 6 groups.


METHODS
The test implants were treated with either a single or daily injections of 200 ng of TNF-alpha. The samples were collected 4 and/or 7 days postoperatively.


METHODS
Pro alpha 1 (I) and pro alpha 1 (III) collagen mRNA concentrations, hydroxyproline, nitrogen, uronic acids, and hexosamine content of the sponge; and ingrowth of new granulation tissue into the sponge.


RESULTS
A single application of TNF-alpha resulted in no significant differences between the groups. After daily applications of TNF-alpha the accumulation of collagen hydroxyproline and volume of ingrowth of granulation tissue were significantly lower than in the controls. After 7 days there were significant reductions in the concentrations of RNA-ribose, nitrogen, and uronic acids. Daily injections of TNF-alpha reduced pro alpha 1 (I) collagen mRNA concentrations but those of pro alpha 1 (III) collagen mRNA levels were not lowered to the same extent.


CONCLUSIONS
Repeated application of TNF-alpha was required to reduce the synthesis of collagen. This down-regulation was selective as pro alpha 1 (I) collagen mRNA concentrations were lowered more than those of pro alpha 1 (III) collagen mRNA.
Rapala
K
K
Department of Surgery, University of Turku, Finland.
Peltonen
J
J
Heino
J
J
Kujari
H
H
Pujol
J P
JP
Niinikoski
J
J
Laato
M
M
D000818:Animals; D003094:Collagen / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006099:Granuloma; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen