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KMID : 0613820190290111251
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Journal of Life Science
2019 Volume.29 No. 11 p.1251 ~ p.1257
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Molecular Mechanisms Involved in Peptidoglycan-induced Expression of Tumor Necrosis Factor-α in Monocytic Cells
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Jeong Ji-Yeong
Son Yong-Hae
Kim Bo-Young
Kim Koan-Hoi
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Abstract
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Peptidoglycan (PG) is found in atheromatous lesions of arteries, where monocytes/macrophages express inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α). This study investigated the effects of PG on TNF-α expression and examined possible cellular factors involved in TNF-α upregulation. The overall aim was to identify the molecular mechanisms underlying inflammatory responses to bacterial pathogen-associated molecular patterns in the artery. Exposure of human THP-1 monocytic cells to PG enhanced the secretion of TNF-α and induced its gene transcription. Inhibition of TLR-2/4 with OxPAPC significantly inhibited TNF-α gene expression, whereas inhibition of LPS by polymyxin B did not. The PG-induced expression of TNF-α was also significantly suppressed by pharmacological inhibitors that modulate activities of cellular signaling molecules; for example, U0126 (an ERK inhibitor), SB202190 (a p38 MAPK inhibitor), and SP6001250 (a JNK inhibitor) significantly attenuated PG-induced transcription of TNF-α and secretion of its gene product. TNF-α expression was also inhibited by rapamycin (an mTOR inhibitor), LY294002 (a PI3K inhibitor), and Akt inhibitor IV (an Akt inhibitor). ROS-regulating compounds, like NAC and DPI, also significantly attenuated TNFα expression induced by PG. These results suggest that PG induces TNF-α expression in monocytes/macrophages by multiple molecules, including TLR-2, PI3K, Akt, mTOR, MAPKs, and ROS.
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KEYWORD
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Gene expression, monocytic cells, peptidoglycan, signaling molecules, tumor necrosis factor-α
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