Sci. Signal., 17 September 2013
Lipoxygenase, CREB, and AtherosclerosisThe chronic inflammatory disease atherosclerosis is characterized by thickening of the arterial wall through the accumulation of lipid-laden foam cells derived from macrophages and smooth muscle cells. It is thought that lipoxygenases (LOs), which metabolize polyunsaturated fatty acids, play key roles in the pathogenesis of atherosclerosis by oxidizing low-density lipoprotein (LDL). Kotla et al. found that the major 12/15-LO product in mice, 15(S)-HETE, stimulated the production of reactive oxygen species in monocytes and macrophages, which culminated in production of the proinflammatory cytokine interleukin-17A (IL-17A) in a manner dependent on the transcription factor CREB. Loss of the gene encoding 12/15-LO in a mouse model of atherosclerosis resulted in decreased accumulation of macrophages at atherosclerotic lesions, decreased fat deposits, and reduced abundance of IL-17A. Together, these data suggest that 12/15-LO exacerbates atherosclerosis in vivo by stimulating the CREB-dependent production of IL-17A and enhancing inflammation.
Citation: S. Kotla, N. K. Singh, M. R. Heckle, G. J. Tigyi, G. N. Rao, The Transcription Factor CREB Enhances Interleukin-17A Production and Inflammation in a Mouse Model of Atherosclerosis. Sci. Signal. 6, ra83 (2013).
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