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.
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.
Iba
Yoshinori
Y
Department of Pathophysiological Science, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata 573-0101, Japan.
Shirai
Maiko
M
Dei
Chiaki
C
Hirata
Takahiro
T
Harada
Chika
C
Masukawa
Tohru
T
D000818:Animals; D015153:Blotting, Western; D015550:Cell Degranulation / Q000187:drug effects; D004431:Ear, External / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D051379:Mice; D013755:Tetradecanoylphorbol Acetate; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis*
D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate