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.

DESIGN

Animal experiment.

SETTING

University Hospital, Finland.

MATERIAL

48 rats in 6 groups.

INTERVENTIONS

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.

MAIN OUTCOME MEASURES

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.

CONCLUSION

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.