Minocycline modulates cytokine and chemokine production in lipopolysaccharide-stimulated THP-1 monocytic cells by inhibiting I¦ÊB kinase ¦Á/¦Â phosphorylation

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• 作者：Katsunori Tai^a ; Hiromichi Iwasaki^b ; ^{hiwasaki@u-fukui.ac.jp} ; Satoshi Ikegaya^a ; Takanori Ueda^a
• 关键词：ERK1/2 ; extracellular signal-regulated kinase 1/2 ; IFN-¦Ã ; interferon-¦Ã ; IKK¦Á/¦Â ; I¦ÊB kinase ¦Á/¦Â ; IL-6 ; interleukin-6 ; IP-10 ; interferon inducible protein ; I¦ÊB¦Á ; inhibitor of nuclear factor-¦ÊB alpha ; JNK ; c-Jun N-terminal kinase ; LPS ; lipopolysacc
• 刊名：Translational Research
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：161
• 期：2
• 页码：99-109
• 全文大小：576 K

文摘

Minocycline, which is a member of the broad-spectrum bacteriostatic tetracycline antibiotics group, has also recently been shown to have additional effects that are separate from their antimicrobial function; however, the detailed mechanisms involved remain unknown. We examined the effects of minocycline on cytokine and chemokine production and the expression levels of intracellular phosphorylated proteins in a lipopolysaccharide (LPS)-induced cytokine response model in?vitro. In the present study, 3 cytokines (tumor necrosis factor [TNF]-¦Á, interleukin [IL]-6, and interferon [IFN]-¦Ã) and 7 chemokines (IL-8, interferon inducible protein [IP]-10, monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein [MIP]-1¦Á, MIP-1¦Â, regulated upon activation normal T-cell expressed secreted [RANTES], and eotaxin) were suppressed by minocycline in a dose-dependent manner. Moreover, the phosphorylation of inhibitor of nuclear factor-¦ÊB alpha (I¦ÊB¦Á) and I¦ÊB kinase (IKK)¦Á/¦Â, which is located upstream from I¦ÊB¦Á, was significantly suppressed by minocycline, whereas the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK), p38, and TGF-¦Â-activated kinase (TAK)1 were not affected. Thus, minocycline appears to inhibit the signaling pathway at the level of IKK¦Á/¦Â phosphorylation. In conclusion, minocycline was found to reduce the production of multiple cytokines and chemokines by inhibiting LPS-induced IKK¦Á/¦Â phosphorylation. That is, minocycline appears to be a potent inhibitor of IKK¦Á/¦Â phosphorylation. From a clinical and translational significance point-of view, these findings suggest that the use of minocycline offers the advantage of providing both antimicrobial and anti-inflammatory effects, which may be key in treating certain types of infectious diseases, particularly those that lead to hypercytokinemia and chronic inflammatory disorders.