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Human Cathelicidin Peptide LL-37 Induces Cell Death in Autophagy-Dysfunctional Endothelial Cells
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this in vitro study using human umbilical vein endothelial cells (HUVECs), researchers examined effects of the antimicrobial peptide LL-37 on autophagy. LL-37 was reported to upregulate LC3-II and increase LC3-positive puncta, and was associated with p62, a protein that recognizes ubiquitinated proteins for autophagosome delivery. Degradation of LL-37 was delayed, and LL-37 was associated with cell death and protein aggregate formation in atg7 knockdown cells with impaired autophagy. The authors state these observations suggest LL-37 induces autophagy in endothelial cells but is linked to increased cell death when autophagy is dysfunctional, and note this may relate to how LL-37 acts on endothelial cells in atherosclerosis.
Abstract
Human cathelicidin LL-37 is an antimicrobial peptide that has a broad spectrum of antimicrobial activities but also acts on host cells to exert immunomodulatory functions. It has been suggested that the increase of LL-37 in atherosclerotic aortas and the dysregulated autophagy of endothelial cells are involved in the pathogenesis of atherosclerosis. In this study, to elucidate the role of LL-37 in atherosclerosis, we investigated the effect of LL-37 on autophagy in endothelial cells using HUVECs. First, LL-37 upregulated LC3-II (an autophagosomal membrane marker) and enhanced the formation of LC3-positive puncta in the cells, suggesting that LL-37 induces autophagy in endothelial cells. Second, LL-37 was associated with p62, which recognizes ubiquitinated proteins and transfers them to autophagosomes, suggesting that LL-37 is ubiquitinated and recognized by p62. Third, the degradation of LL-37 was delayed, and LL-37 induced cell death in atg7 knockdown cells, which was accompanied by the formation of protein aggregates in the cells. Taken together, these observations suggest that LL-37 induces autophagy in endothelial cells but enhances cell death in autophagy-dysfunctional conditions, in which the intracellular degradation of LL-37 is disturbed. Thus, LL-37 may exert an adverse action on autophagy-dysfunctional endothelial cells to induce cell death in the pathogenesis of atherosclerosis.
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