Inhibitory effects of bisbenzylisoquinoline alkaloids on induction of proinflammatory cytokines, interleukin-1 and tumor necrosis factor-alpha.
Bisbenzylisoquinoline alkaloids are known to affect immune responses as well as inflammatory responses, and have been used for the treatment of inflammatory symptoms in China. This study is aimed at elucidating the inhibitory effects of two alkaloids, fangchinoline and isotetrandrine, on the induction of the proinflammatory cytokines, interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-alpha), by Staphylococcus aureus Cowan 1 (SAC)-stimulated human peripheral blood mononuclear cells. These two alkaloids inhibited cytokine production in a dose-dependent manner, and they inhibited it by more than 90% at 10 micrograms/ml at every time point examined. Of note was that these two alkaloids appeared to inhibit IL-1 beta production more effectively than IL-1 alpha production. When the levels of cytokine mRNA were measured by semiquantitative RT-PCR, these alkaloids reduced the levels of the mRNAs of IL-1 beta and TNF-alpha, but not that of beta 2-microglobulin, suggesting that these alkaloids may suppress cytokine transcription selectively.
Onai
N
N
Department of Biomolecular Science, Toho University, Chiba, Japan.
Tsunokawa
Y
Y
Suda
M
M
Watanabe
N
N
Nakamura
K
K
Sugimoto
Y
Y
Kobayashi
Y
Y
D000470:Alkaloids / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001483:Base Sequence; D044182:Benzylisoquinolines; D017931:DNA Primers; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D044182:Benzylisoquinolines; D017931:DNA Primers; D004365:Drugs, Chinese Herbal; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C009438:tetrandrine; C060802:fangchinoline