Restraint of Proinflammatory Cytokine Biosynthesis by Mitogen-Activated Protein Kinase Phosphatase-1 in Lipopolysaccharide-Stimulated Macrophages

• DOI: 10.4049/jimmunol.169.11.6408
• Publication Date: 2014-04-20T23:41:24Z
• Authors: Peili Chen; Ji Li; Janice Barnes; Gertrude C. Kokkonen; John C. Lee; Yusen Liu
• Keywords: Proinflammatory cytokine

Exposure of macrophages to LPS elicits the production proinflammatory cytokines, such as TNF-alpha, through complex signaling mechanisms. Mitogen-activated protein (MAP) kinases play a critical role in this process. In present study, we have addressed MAP kinase phosphatase-1 (MKP-1) regulating cytokine using RAW264.7 macrophages. Analysis activity revealed transient activation c-Jun N-terminal (JNK) and p38 after stimulation. Interestingly, MKP-1 was induced concurrently with inactivation JNK p38, whereas blocking induction by triptolide prevented inactivation. Ectopic expression accelerated substantially inhibited TNF-alpha IL-6. Induction found be extracellular signal-regulated dependent involved enhanced gene increased stability. Finally, also glucocorticoids well cholera toxin B subunit, an agent capable preventing autoimmune diseases animal models. These findings highlight negative regulator macrophage inflammatory response, underscoring its premise potential target for developing novel anti-inflammatory drugs.