title: Minocycline modulates cytokine and chemokine production in lipopolysaccharide-stimulated THP-1 monocytic cells by inhibiting IκB kinase α/β phosphorylation.
abstract: 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]-α, interleukin [IL]-6, and interferon [IFN]-γ) and 7 chemokines (IL-8, interferon inducible protein [IP]-10, monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein [MIP]-1α, MIP-1β, 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-κB alpha (IκBα) and IκB kinase (IKK)α/β, which is located upstream from IκBα, 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-β-activated kinase (TAK)1 were not affected. Thus, minocycline appears to inhibit the signaling pathway at the level of IKKα/β phosphorylation. In conclusion, minocycline was found to reduce the production of multiple cytokines and chemokines by inhibiting LPS-induced IKKα/β phosphorylation. That is, minocycline appears to be a potent inhibitor of IKKα/β 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.
authors.affiliation: First Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tai
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ikegaya
authors.forename: Takanori
authors.initials: T
authors.lastname: Ueda
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018925:Chemokines / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008911:Minocycline / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation
chemical_list: D000900:Anti-Bacterial Agents; D018925:Chemokines; D008070:Lipopolysaccharides; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; D008911:Minocycline