Bacterial lipopolysaccharide and antimicrobial LL-37 enhance ICAM-1 expression and NF-κB p65 phosphorylation in senescent endothelial cells
- Kaori Suzuki
- Mari Ohkuma
- Isao Nagaoka
Affiliations: Department of Host Defense and Biochemical Research, Juntendo University Graduate School of Medicine, Tokyo 113‑8421, Japan
- Published online on: July 31, 2019 https://doi.org/10.3892/ijmm.2019.4294
Copyright: © Suzuki
et al. This is an open access article distributed under the
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Commons Attribution License.
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Cellular senescence is associated with the induction of a proinflammatory phenotype. Notably, senescent endothelial cells are detected at the sites of atherosclerotic lesions, suggesting the involvement of senescent endothelial cells in atherogenesis. Moreover, bacterial infection has been speculated to contribute to the pathogenesis of atherosclerosis. The present study investigated the effects of Gram‑negative bacterial lipopolysaccharide (LPS) and LL‑37 (a human antimicrobial peptide of the cathelicidin family), on senescent endothelial cells, using serially passaged human endothelial cells. The results indicated that senescent endothelial cells exhibited the basal proinflammatory phenotype, as evidenced by higher intercellular adhesion molecule‑1 (ICAM‑1) expression and NF‑κB p65 phosphorylation, compared with non‑senescent cells. Additionally, exposure to LPS and LL‑37 further enhanced the expression of ICAM‑1 in senescent endothelial cells, compared with non‑senescent cells. Of note, the NF‑κB p65 pathway was more activated in senescent endothelial cells stimulated with LPS and LL‑37. Furthermore, the expression levels of the receptors for LPS and LL‑37 [toll‑like receptor 4 (TLR4) and purinergic receptor P2X 7 (P2X7), respectively] were upregulated in senescent endothelial cells. These observations indicated that LPS and LL‑37 enhanced the ICAM‑1 expression and NF‑κB p65 activation in senescent endothelial cells, potentially via the upregulated TLR4 and P2X7. Thus, senescent endothelial cells may contribute to the pathogenesis of atherosclerosis via the basal proinflammatory phenotype and the enhanced inflammatory responses against atherogenic factors, including LPS and LL‑37.