RRC ID |
42759
|
著者 |
Hirasawa N, Torigoe M, Ohgawara R, Murakami A, Ohuchi K.
|
タイトル |
Involvement of MAP kinases in lipopolysaccharide-induced histamine production in RAW 264 cells.
|
ジャーナル |
Life Sci
|
Abstract |
Roles of mitogen-activated protein (MAP) kinases in lipopolysaccharide (LPS)-induced production of histamine in the mouse macrophage-like cell line RAW 264 were analyzed. Incubation of RAW 264 cells in the presence of LPS increased histamine levels in the conditioned medium in a concentration- and time-dependent manner. The levels of histidine decarboxylase (HDC) mRNA and the 74-kDa HDC protein were also increased at 4 to 8 h and 8 to 12 h, respectively. LPS elicited the phosphorylation of p44/42 MAP kinase, p38 MAP kinase, and c-Jun N-terminal kinase (JNK). The MAP kinase-Erk kinase 1 inhibitor U0126 (0.1-10 microM) suppressed the LPS-induced phosphorylation of p44/42 MAP kinase, and inhibited the LPS-induced production of histamine and expression of the HDC mRNA and 74-kDa HDC protein in a concentration-dependent manner. The JNK inhibitor SP600125 (3-30 microM) suppressed the LPS-induced phosphorylation of c-Jun, and inhibited the LPS-induced production of histamine and expression of the HDC mRNA and 74-kDa protein in a concentration-dependent manner. Combined treatment with U0126 (0.3 microM) and SP600125 (10 microM) inhibited the LPS-induced production of histamine additively. The p38 MAP kinase inhibitor SB203580 (0.1-10 microM) partially inhibited the LPS-induced production of histamine. These findings suggest that LPS increases histamine production in RAW 264 cells by inducing the expression of the 74-kDa HDC protein, and that the LPS-induced expression of HDC is up-regulated at the transcriptional level by MAP kinases, especially p44 MAP kinase and JNK.
|
巻・号 |
80(1)
|
ページ |
36-42
|
公開日 |
2006-12-3
|
DOI |
10.1016/j.lfs.2006.08.019
|
PII |
S0024-3205(06)00656-4
|
PMID |
16978663
|
MeSH |
Animals
Anthracenes / pharmacology
Butadienes / pharmacology
Cell Line
Extracellular Signal-Regulated MAP Kinases / physiology
Histamine / biosynthesis*
Histidine Decarboxylase / analysis
Histidine Decarboxylase / genetics
Imidazoles / pharmacology
JNK Mitogen-Activated Protein Kinases / physiology
Lipopolysaccharides / pharmacology*
Macrophages / metabolism*
Mice
Mitogen-Activated Protein Kinases / physiology*
Nitriles / pharmacology
Phosphorylation
Pyridines / pharmacology
RNA, Messenger / analysis
p38 Mitogen-Activated Protein Kinases / physiology
|
IF |
3.647
|
引用数 |
9
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
PHARMACOLOGY & PHARMACY
|
リソース情報 |
ヒト・動物細胞 |
RAW 264(RCB0535) |