Involvement of mast cells in the regulation of matrix metalloproteinase-9 and tissue inhibitor of metalloproteases-1 in 12-O-tetradecanoylphorbolacetate-induced inflammation in mice.

Abstract

In this study, we investigated the involvement of mast cells in the regulation of matrix metalloproteinase-9 (MMP-9) in 12-O-tetradecanoylphorbolacetate (TPA)-induced inflammation, using mast cell-deficient (W/W(v)) mice and control (+/+) mice. Topical application of TPA to the ears induced acute inflammation, accompanied by mast cell degranulation in +/+ mice, which peaked at 6-12 h. There was no significant difference in ear thickness between the groups until 12 h, but the swelling was greater in W/W(v) mice than +/+ mice at 24-36 h. Western blot analysis revealed that TPA-induced marked increases in levels of proMMP-9 and tissue inhibitor of metalloproteinases-1 (TIMP-1), which existed as complexes with proMMP-9. The amount of proMMP-9-TIMP-1 complex was markedly smaller in +/+ mice than W/W(v) mice at 6 and 24 h, but had almost returned to control levels in both groups at 48 h. The free form of proMMP-9 was also slightly less abundant in +/+ mice than W/W(v) mice at 6, 24, and 48 h. Gelatin zymographic analysis revealed that levels of the active species of MMP-9 (approximately 74 and 83 kD), as well as free form of proMMP-9, increased time-dependently after the application of TPA and peaked at 24 h in +/+ mice. The 74-kD band was detected only in +/+ mice at 6 h. Our results therefore suggested that during inflammation degranulation of mast cells results in a reduction of the proMMP-9-TIMP-1 complex levels, together with a fall in the amount of free proMMP-9.

• Authors: Yoshinori Iba, Maiko Shirai, Chiaki Dei, Takahiro Hirata, Chika Harada, Tohru Masukawa
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 7 Issue 5 Pg. 597-603 (May 2007) ISSN: 1567-5769 [Print] Netherlands
• PMID: 17386407 (Publication Type: Journal Article)

Chemical References

• Tissue Inhibitor of Metalloproteinase-1
• Matrix Metalloproteinase 9
• Tetradecanoylphorbol Acetate

Topics

• Animals
• Blotting, Western
• Cell Degranulation (drug effects)
• Ear, External (pathology)
• Inflammation (chemically induced, enzymology, metabolism)
• Mast Cells (drug effects, physiology)
• Matrix Metalloproteinase 9 (biosynthesis)
• Mice
• Tetradecanoylphorbol Acetate
• Tissue Inhibitor of Metalloproteinase-1 (biosynthesis)