Inhibitory effect of ferulic acid on macrophage inflammatory protein-2 production in a murine macrophage cell line, RAW264.7.
We investigated time-related productions of certain cytokines in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, a murine macrophage cell line, by enzyme-linked immunosorbent assay. Macrophage inflammatory protein-2 (MIP-2) levels became detectable after 2 h and markedly increased over the first 8 h. Thereafter, this level remained at the same level between 10 and 16 h, and then increased again until 24 h, showing a tendency of biphasic pattern. Tumour necrosis factor (TNF)-alpha was detectable at 2 h and then increased sharply until 6 h at which it attained its peak. A low but recognizable level of interleukin (IL)-1alpha/beta was also detectable. When the inhibitory effect of ferulic acid (FA), an active component of the Rhizoma of Cimicifuga sp. used frequently as anti-inflammatory drug in Japanese Oriental medicines, was compared with that of dexamethasone (DX) on MIP-2 and TNF-alpha productions in response to LPS, both FA and DX could reduce the production of these cytokines in a dose-dependent manner. Concerning TNF-alpha, however, the inhibitory effect of FA was very weak compared with that of DX. In addition, FA as well as DX reduced MIP-2 production induced by TNF-alpha. These data suggest that MIP-2 might be induced by a direct effect of LPS and in part indirect one via initial induction of other cytokines such as TNF-alpha, leading a tendency of biphasic pattern. Comparing DX, FA is considered to be a novel and unique drug inhibiting MIP-2 production more selectively.
Sakai
S
S
Department of Japanese Oriental Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Sugitani.
Ochiai
H
H
Nakajima
K
K
Terasawa
K
K
D000818:Animals; D002460:Cell Line; D054426:Chemokine CXCL2; D003373:Coumaric Acids / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D015846:Monokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology
D054426:Chemokine CXCL2; D003373:Coumaric Acids; D008070:Lipopolysaccharides; D015846:Monokines; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; C004999:ferulic acid