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Immunology. 2020 Feb;159(2):221-230. doi: 10.1111/imm.13142. Epub 2019 Nov 21.

Highly oxidized low-density lipoprotein mediates activation of monocytes but does not confer interleukin-1β secretion nor interleukin-15 transpresentation function.

Author information

1
Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
2
Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
3
Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, Ohio State University, Columbus, OH, USA.

Abstract

Oxidized low-density lipoprotein (LDL) contributes to cardiovascular disease in part by mediating activation and maturation of monocytes and macrophages. Furthermore, co-localization studies using histochemical approaches have implicated a potential role for oxidized LDL as a mediator of interleukin-15 (IL-15) expression in myeloid cells of atherosclerotic plaque. The latter activity could be an important pro-inflammatory mechanism that mediates myeloid cell/T-cell crosstalk. Here, we examined the responses of primary human monocytes to highly oxidized LDL molecules. Oxidized LDL readily induced secretion of chemokines MCP-1 (CCL2) and GRO-α (CXCL1) but unlike lipopolysaccharide (LPS), has limited capacity to induce a variety of other cytokines including tumor necrosis factor-α, IL-6, IL-1β and interferon-γ-induced protein-10 and also displayed a poor capacity to induce p-Akt or P-S6 signaling. Failure of oxidized LDL to induce IL-1β secretion was associated with limited induction of caspase-1 activation. Furthermore, despite finding evidence that oxidized LDL could enhance the expression of IL-15 and IL-15 receptor expression in monocytes, we found no evidence that it could confer IL-15 transpresentation capability to these cells. This observation contrasted with induction of IL-15 transpresentation in lipopolysaccharide-stimulated monocytes. Overall, our data suggest that highly oxidized LDL is a selective inducer of monocyte activation. Sterile inflammatory mediators, particularly those implicated in Toll-like receptor 4 signaling, may play a role in vascular pathology but the activities of these agents are not uniform.

KEYWORDS:

interleukin-15; monocytes; oxidized low-density lipoprotein

PMID:
31663113
PMCID:
PMC6954695
[Available on 2021-02-01]
DOI:
10.1111/imm.13142
[Indexed for MEDLINE]

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