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Molecular interaction of NFκB and NICD in monocyte–macrophage differentiation is a target for intervention in atherosclerosis

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Journal of Cellular Physiology

Published online on


--- - |2- Inhibition of NFκB regulated notch intracellular domain (NICD), which, in turn, downturned macrophage differentiation. Inhibition of both NFκB–NICD is a potential target for intervention in early stage of atherosclerosis (monocyte to macrophage differentiation), to prevent the furtherance of disease. Abstract The activation of two transcription factors, NFκB and NICD (notch intracellular domain), plays a crucial role in different stages of atherosclerotic disease progression, from early endothelial activation by modified lipids like oxidized low‐density lipoprotein (oxyLDL) to the imminent rupture of the atherosclerotic plaque. Inflammatory mediators and the notch pathway proteins were upregulated in atherogenic diet‐induced rats and the same was confirmed by the differentiation of monocyte to macrophage on exposure to oxyLDL. The inflammatory transcription factor NFκB and the notch signaling transcription factor NICD were analysed for their molecular interaction in monocyte to macrophage differentiation. Inhibition of NFκB by dexamethasone in monocyte to macrophage differentiation resulted in a concomitant downregulation of NICD, whereas inhibition of NICD by N‐(N‐[3, 5‐difluorophenacetyl])‐l‐alanyl)‐S‐phenylglycine t‐butyl ester (DAPT), a γ–secretase inhibitor, did not significantly influence the expression of NFκB, but downregulated macrophage differentiation. These findings revealed that NFκB inhibition using dexamethasone regulated NICD, which turned down macrophage differentiation. Thus, inhibition of both NFκB–NICD is a potential target for intervention in atherosclerosis. - 'Journal of Cellular Physiology, EarlyView. '