Regulation of interleukin-1alpha and tumor necrosis factor-alpha-induced interleukin-8 production by amnion-derived (WISH) cells.
OBJECTIVE
It has been reported that interleukin (IL)-8 is produced in the amnion and that its production is enhanced by the initiation of labor. The purpose of this study was to clarify the mechanism of IL-8 production by amnion-derived (WISH) cells.


METHODS
Cells were cultured and treated with various concentrations of interleukin (IL)-1alpha, IL-1 receptor antagonist (ra), tumor necrosis factor (TNF)- alpha, C2-, C6-ceramide, mitogen-activated protein (MAP) kinase kinase (MEK) inhibitor (U0126) and pyridinyl imidazole (p38 MAP kinase inhibitor, SB203580). IL-8 in the culture medium was measured by ELISA.


RESULTS
The production of IL-8 was significantly increased by IL-1alpha or TNF-alpha, and the increase of IL-8 stimulated by IL-1alpha was suppressed by IL-1 ra in a dose-dependent manner. The increase in IL-8 production by IL-1alpha or TNF-alpha was further enhanced by simultaneous addition of C2-ceramide. The increase of IL-8 stimulated by IL-1alpha or TNF-alpha was also suppressed by treatment with U0126 or SB203580. The results of this study demonstrate that the production of IL-8 induced by IL-1alpha and TNF-alpha is enhanced by C2-ceramide, and suppressed by MEK inhibitor or P38 MAP kinase inhibitor.


CONCLUSIONS
The results suggest that ceramide-mediated accumulation and MAP kinase-mediated suppression of inflammatory events in the amnion may play an important role in the maintenance of pregnancy and initiation of labor.
Department of Obstetrics and Gynecology, Oita University, Faculty of Medicine, Yufu, Oita, Japan. kawayas@oita-u.ac.jp
Y
Y
Kawano
Y
Y
Furukawa
S
S
Karakida
N
N
Kira
T
T
Ishii
H
H
Narahara
D000650:Amnion / Q000378:metabolism*; D002070:Butadienes; D002460:Cell Line; D004791:Enzyme Inhibitors; D037341:Fumonisins; D006801:Humans; D007093:Imidazoles; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D053582:Interleukin-1alpha / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009570:Nitriles; D011725:Pyridines; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D002070:Butadienes; C508606:CXCL8 protein, human; D004791:Enzyme Inhibitors; D037341:Fumonisins; C508584:IL1A protein, human; C507763:IL1RN protein, human; D007093:Imidazoles; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D016209:Interleukin-8; C064769:N-acetylsphingosine; D009570:Nitriles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; C113580:U 0126; C056933:fumonisin B1; D020928:Mitogen-Activated Protein Kinases; D013110:Sphingosine; C093642:SB 203580