Abstract | BACKGROUND: Interleukin-6-deficient (IL-6KO) mice display significantly delayed cutaneous wound healing characterized by decreased re-epithelialization, granulation tissue and wound closure. Dermal fibroblasts are one of the principal cell types found in granulation tissue and mediate numerous processes during healing. OBJECTIVES: To investigate the effects that IL-6 might have on granulation tissue formation and fibroblast motility. As fibroblast motility is associated with matrix metalloproteinase ( MMP) activity, the expression of MMP-2 and the tissue inhibitors of metalloproteinase (TIMP)-1 and -2 were assessed. METHODS: Punch biopsies (4 mm) were performed in the skin of IL-6KO and C57BL/6 mice. The expression of MMP-2, TIMP-1 and -2 in wound tissue was monitored over time. Cellular infiltration and granulation tissue formation was monitored by subcutaneous implantation of polyvinyl alcohol (PVA) sponges. A free-floating collagen lattice model was also used to investigate the direct effects of IL-6 treatment on isolated IL-6KO fibroblasts. The expression of MMP-2, and the inhibitors TIMP-1 and -2, were assessed via real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: IL-6KO wounds showed impaired granulation tissue formation 5 days postwounding and fewer fibroblasts had populated the PVA matrices 7 days after implantation in IL-6KO mice compared with wild-type C57BL/6. The mRNA and protein expression of MMP-2 and TIMP-2 mRNA was increased in IL-6KO mice compared with wild-type mice beyond 1 day postwounding, while the expression of TIMP-1 mRNA was transiently higher in IL-6KO only 3 days postwounding. Treatment of collagen lattices with various concentrations of rmIL-6 again showed a dose-response decrease in mRNA and protein expression of MMP-2 and TIMP-2 protein expression, compared with saline control, while TIMP-1 did not appear to be significantly modulated. CONCLUSIONS: These results indicate that IL-6 influences the function of fibroblasts in wounds, and one mechanism of this regulation may be through the modulation of MMP-2 and TIMP proteins.
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Authors | L R Luckett, R M Gallucci |
Journal | The British journal of dermatology
(Br J Dermatol)
Vol. 156
Issue 6
Pg. 1163-71
(Jun 2007)
ISSN: 0007-0963 [Print] England |
PMID | 17441960
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Interleukin-6
- Tissue Inhibitor of Metalloproteinase-1
- Tissue Inhibitor of Metalloproteinase-2
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 1
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Topics |
- Animals
- Cell Movement
(drug effects)
- Fibroblasts
(physiology)
- Granulation Tissue
(cytology, metabolism)
- Interleukin-6
(deficiency, genetics, therapeutic use)
- Matrix Metalloproteinase 1
(metabolism)
- Matrix Metalloproteinase 2
(metabolism)
- Mice
- Mice, Inbred C57BL
- Tissue Inhibitor of Metalloproteinase-1
(metabolism)
- Tissue Inhibitor of Metalloproteinase-2
(metabolism)
- Wound Healing
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