Katsuyuki Mishima1, Hitomi Otani1, Takatoshi Tanabe2,
Hiroshi Kawasaki1, Akihiro Oshiro1, Naoaki Saito3,
Ryokei Ogawa2 and Chiyoko Inagaki1,*
1Department of Pharmacology, and 2Department of
Orthopaedic Surgery, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi
City, Osaka 570-8506, Japan
3Laboratory of Molecular Pharmacology, Biosignal Research Center,
Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan
*Corresponding author. FAX: +81-6-6992-2940
E-mail: inagaki@takii.kmu.ac.jp
Abstract: The sympathetic nervous system has been indicated to influence
the severity of inflammatory disease including rheumatoid arthritis. In
this study, we elucidated the effects of catecholamine on the synovial cell
populations. Stimulation with epinephrine or norepinephrine for 1-2 weeks
dose- and time-dependently increased the number of synovial A (macrophage-like)
cells but decreased that of B (fibroblast-like) cells. These responses in
A and B cells were inhibited by the a2-antagonist
yohimbine, the G-protein inactivator pertussis toxin and the phospholipase
C (PLC) inhibitor U-73122. Furthermore, the protein kinase C (PKC) inhibitor
calphostin C and mitogen-activated protein (MAP) kinase inhibitors PD98059
and wortmannin also abolished the norepinephrine effects on A and B cell
numbers. In A cells cloned from an A and B cell mixture, norepinephrine
also increased the cell number. In immunoblotting and immunocytostaining
analyses, among the PKC isozymes, only PKC bII
immunoreactivity was observed in the cytoplasm of unstimulated A and B cells.
After a2-adrenoceptor stimulation, PKC
bII immunoreactivity increased in the plasma membranes
of both A and B cells with decreases in the cytoplasm. These findings indicated
that a2-adrenoceptor stimulation of
type A and B synoviocytes produced an increase and a decrease in the respective
cell number, probably through Gi-coupled PLC activation and the resulting
stimulation of the PKC bII/MAP kinase.
Keywords: Synoviocyte, a2-Adrenoceptor
stimulation, Cell population, Protein kinase C bII
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