title: Rho-kinase regulates prostaglandin D(2)-stimulated heat shock protein 27 induction in osteoblasts.
abstract: We previously reported that prostaglandin D(2) (PGD(2)) stimulates heat shock protein 27 (HSP27) induction through p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. In addition, we recently showed that PGD(2) activates Rho-kinase, resulting in the regulation of interleukin-6 synthesis via activation of p38 MAP kinase but not p44/p42 MAP kinase in these cells. In the present study, in order to investigate whether Rho-kinase is involved in the PGD(2)-stimulated HSP27 induction in MC3T3-E1 cells, we examined the effects of Rho-kinase inhibitors on HSP27 induction. Y27632 and fasudil, Rho-kinase inhibitors, markedly suppressed the HSP27 induction stimulated by PGD(2) in a dose-dependent manner without affecting levels of HSP70 in the presence of PGD(2). Immunofluorescence microscopy studies also revealed that Y27632 and fasudil markedly suppressed the induction of HSP27. Y27632 and fasudil attenuated the PGD(2)-induced phosphorylation levels of SAPK/JNK. In conclusion, Rho-kinase inhibitors regulate PGD(2)-stimulated HSP27 induction via activation of both SAPK/JNK and p38 MAP kinase in osteoblasts.
authors.affiliation: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601; ; Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194;
authors.forename: Kenji
authors.initials: K
authors.lastname: Kato
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
authors.forename: Hideo
authors.initials: H
authors.lastname: Natsume
authors.forename: Seiji
authors.initials: S
authors.lastname: Adachi
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.forename: Chiho
authors.initials: C
authors.lastname: Minamitani
authors.forename: Jun
authors.initials: J
authors.lastname: Mizutani
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otsuka