Human β-defensin-3 alleviates the progression of atherosclerosis accelerated byPorphyromonas gingivalislipopolysaccharide

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Abstract

Background and aim:

Porphyromonas gingivalis (P.gingivalis) lipopolysaccharide (LPS) is reported to be associated with the progression of atherosclerosis (AS). In this study, we explored the potential of human β-defensin-3 (hBD3), an antimicrobial peptide with immunomodulatory properties, to alleviate AS progression accelerated by P.gingivalis LPS and the mechanism underlying this effect.

Materials and methods:

Apolipoprotein E-deficient mice were injected intraperitoneally with hBD3, P.gingivalis LPS, or hBD3 + P.gingivalis LPS. The aorta was assessed immunohistologically and mRNA levels of inflammatory cytokines were determined by quantitative PCR. Macrophages and vascular endothelial cells were stimulated in vitro to investigate the hBD3 target cells. Inflammatory cytokines in serum and cell culture supernatants were detected using cytometric bead arrays. Signaling pathways were investigated by Western blotting.

Results:

In P.gingivalis LPS-treated mice, hBD3 significantly reduced serum IL-6 and TNF-α levels and aortic expression of ICAM-1, IL-6, and MCP-1 (mRNA and protein). The area and severity of atherosclerotic lesions were also diminished, with less advanced plaque formation, more continuous and distinct elastic lamina, and more normal smooth muscle cells arranged along the tunica media layer. In vitro, hBD3 decreased TNF-α, IL-1β, IL-6 secretion and downregulated TNF-α, IL-1β, IL-6, IL-8, VCAM-1, and IL-10 mRNA levels in macrophages. hBD3 did not influence TNF-α, IL-6, and IL-8 levels in HUVECs culture supernatants. Furthermore, hBD3 suppressed P.gingivalis LPS-induced activation of the NF-κB, p38 and JNK pathways.

Conclusion:

hBD3 alleviates AS progression accelerated by P.gingivalis LPS in apolipoprotein E-deficient mice by downregulating the cytokine expression in macrophages via the MAPK and NF-κB signaling pathways.

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