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http://dx.doi.org/10.5483/BMBRep.2018.51.6.064

Anti-inflammatory effects of a novel compound, MPQP, through the inhibition of IRAK1 signaling pathways in LPS-stimulated RAW 264.7 macrophages  

Kim, Ba Reum (College of Pharmacy, Chung-Ang University)
Cho, Young-Chang (College of Pharmacy, Chonnam National University)
Cho, Sayeon (College of Pharmacy, Chung-Ang University)
Publication Information
BMB Reports / v.51, no.6, 2018 , pp. 308-313 More about this Journal
Abstract
Small-molecule inhibitors are widely used to treat a variety of inflammatory diseases. In this study, we found a novel anti-inflammatory compound, 1-[(2R,4S)-2-methyl-4-(phenylamino)-1,2,3,4-tetrahydroquinolin-1-yl]prop-2-en-1-one (MPQP). It showed strong anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. These effects were exerted through the inhibition of the production of NO and pro-inflammatory cytokines, such as interleukin (IL)-6, $IL-1{\beta}$, and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$). Furthermore, MPQP decreased the expression levels of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). Additionally, it mediated the inhibition of the phosphorylation of p38, c-Jun N-terminal kinase (JNK), the inhibitor of ${\kappa}B{\alpha}$ ($I{\kappa}B{\alpha}$), and their upstream kinases, $I{\kappa}B$ kinase (IKK) ${\alpha}/{\beta}$, mitogen-activated protein kinase kinase (MKK) 3/6, and MKK4. Furthermore, the expression of IL-1 receptor-associated kinase 1 (IRAK1) that regulates $NF-{\kappa}B$, p38, and the JNK signaling pathways, was also increased by MPQP. These results indicate that MPQP regulates the IRAK1-mediated inflammatory signaling pathways by targeting IRAK1 or its upstream factors.
Keywords
Cyclooxygenase 2; IL-1 receptor-associated kinase 1; Inflammation; Inflammatory cytokine; 1-[(2R,4S)-2-methyl-4-(phenylamino)-1,2,3,4-tetrahydroquinolin-1-yl]prop-2-en-1-one;
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