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KMID : 0613820220320060421
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Journal of Life Science
2022 Volume.32 No. 6 p.421 ~ p.429
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Involvement of Multiple Signaling Molecules in Peptidoglycan-induced Expression of Interleukin-1α in THP-1 Monocytes/Macrophages
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Heo Weon
Son Yong-Hae
Cho Hyok-Rae
Kim Koan-Hoi
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Abstract
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The expression of interleukin-1α (IL-1α) is elevated in monocytic cells, such as monocytes and macrophages, within atherosclerotic arteries, yet the cellular molecules involved in cytokine upregulation remain unclear. Because peptidoglycan (PG), a major component of gram-positive bacterial cell walls, is detected within the inflammatory cell-rich regions of atheromatous plaques, it was investigated if PG contributes to IL-1α expression in monocytes/macrophages. Exposure of THP-1 monocytic cells to PG resulted in elevated levels of IL-1α gene transcripts and increased secretion of IL-1α protein. The transcription and secretion of IL-1α were abrogated by OxPAPC, an inhibitor of TLR2/4, but not by polymyxin B that inhibits lipopolysaccharide-induced TLR4 activation. To understand the molecular mechanisms of the inflammatory responses due to bacterial pathogen-associated molecular patterns (PAMPs) in diseased arteries, we attempted to determine the cellular factors involved in the PG-induced upregulation of IL-1α expression. Pharmacological inhibition of cell signaling pathways with LY294002 (a PI3K inhibitor), Akti IV (an inhibitor of Akt activation), rapamycin (an mTOR inhibitor), U0126 (a MEK inhibitor), SB202190 (a p38 MAPK inhibitor), SP6001250 (a JNK inhibitor), and DPI (a NOX inhibitor) also significantly attenuated the PG-mediated expression of IL-1α. These results suggest that PG induces the monocytic or macrophagic expression of IL-1α, thereby contributing to vascular inflammation, via multiple signaling molecules, including TLR2, PI3K/Akt/mTOR, and MAPKs.
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KEYWORD
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Interleukin-1α, monocytes/macrophages, peptidoglycan, signaling pathways
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