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KMID : 0370220180620050306
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Yakhak Hoeji
2018 Volume.62 No. 5 p.306 ~ p.312
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Anti-inflammatory Effect of Tolerance Induced by Pam3CSK4 in Murine Macrophage RAW 264.7 Cells via Inhibitor of NF-κB/MAPK Signaling Pathway
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Han Sang-Chul
Kang Na-Jin
Park Kyung-Min
Park Ji-Seon
Eum Young-Eun
Kang Hee-Kyoung
Yoo Eun-Sook
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Abstract
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Endotoxin tolerance is an essential mechanism for immune-homeostatic response that suppresses excessive inflammatory cytokine production. It is induced by repeated exposure to endotoxins, such as lipopolysaccharide (LPS). Many recent studies have investigated LPS tolerance, but the molecular mechanism for Pam3CSK4-tolerance in mouse macrophage is poorly understood. Pam3CSK4 binds to TLR1/2 and regulates several downstream signaling pathways, including NF-κB and MAPK pathways. In this study, pretreatment with Pam3CSK4 inhibited TNF-α and IL-6 production after secondary Pam3CSK4 challenge in a time- and dose-dependent manner without cell cytotoxicity. Nontolerized RAW 264.7 cells responded to Pam3CSK4 challenge with the degradation of IκBα and phosphorylation of p38, ERK and JNK. On the other hand, activation of IκBα and MAPKs was diminished in Pam3CSK4-tolerized cells. We also investigated whether pretreatment with Pam3CSK4 regulates the expression of signaling inhibitors TNFAIP3, SOCS1 and SOCS3. Compared with the nontolerized macrophages, the expression of A20, SOCS1 and SOCS3 was increased in Pam3CSK4-tolerized macrophages. These results indicate that Pam3CSK4-tolerized macrophages suppress pro-inflammatory responses and induce the expression of signaling inhibitors of TLR mechanism.
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KEYWORD
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tolerance, Pam3CSK4, TNF-α inducible protein 3, suppressor of cytokine signaling 1/3
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