Involvement of prostaglandins and histamine in nickel wire-induced acute inflammation in mice.
The irritancy of Nickel (Ni) ions has been well documented clinically. However, the chemical mediators involved in the acute inflammation induced by solid Ni are not fully understood. We used the Ni wire-implantation model in mice and examined roles of prostaglandins and histamine in plasma leakage in the acute phase. The subcutaneous implantation of a Ni wire into the back of mice induced plasma leakage from 8 to 24 h and tissue necrosis around the wire at 3 days, whereas the implantation of an aluminum wire induced no such inflammatory responses. An increase in the mRNA for cyclooxygenase (COX)-2 and HDC in cells around the Ni wire was detected 4 h after the implantation. The leakage of plasma at 8 h was inhibited by indomethacin in a dose-dependent manner. Dexamethasone and the p38 MAP kinase inhibitor SB203580 also inhibited the exudation of plasma consistent with the inhibition of the expression of COX-2 mRNA. Furthermore, plasma leakage was partially but siginificantly reduced in histamine H1 receptor knockout mice and histidine decarboxylase (HDC) knockout mice but not in H2 receptor knockout mice. These results suggested that the Ni ions released from the wire induced the expression of COX-2 and HDC, resulting in an increase in vascular permeability during the acute phase of inflammation.
Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan. hirasawa@mail.pharm.tohoku.ac.jp
Noriyasu
N
Hirasawa
Yoshiaki
Y
Goi
Rina
R
Tanaka
Kenji
K
Ishihara
Hiroshi
H
Ohtsu
Kazuo
K
Ohuchi
D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006632:Histamine / Q000737:chemistry*; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis; D009532:Nickel / Q000737:chemistry*; D010539:Permeability; D011453:Prostaglandins / Q000737:chemistry*; D011725:Pyridines / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000235:genetics; D012867:Skin / Q000187:drug effects; D013997:Time Factors
D007093:Imidazoles; D011453:Prostaglandins; D011725:Pyridines; D011969:Receptors, Histamine H1; D009532:Nickel; D006632:Histamine; D051546:Cyclooxygenase 2; C093642:SB 203580