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Endogenous expression of human apolipoprotein E elicits isoform‐dependent effects on macrophage cytokine expression
Author(s) -
Tsoi Lo Ming,
Wong Kin Yee,
Liu Yuet Man,
Ho Yuan Yuan
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a534-c
Subject(s) - apolipoprotein e , cytokine , p38 mitogen activated protein kinases , tumor necrosis factor alpha , endogeny , transfection , macrophage , biology , gene isoform , lipopolysaccharide , microbiology and biotechnology , mapk/erk pathway , cell culture , kinase , endocrinology , medicine , immunology , in vitro , biochemistry , gene , genetics , disease
This study aimed at investigating the effects of endogenous expression of human apoE isoforms on macrophage cytokine expression. There is mounting evidence shown that atherosclerosis is intrinsically an inflammatory process. Macrophages are important inflammatory modulator in atherosclerosis. Many studies have suggested that apoE elicits anti‐atherogenic functions in an isoform‐dependent manner. In this study, mouse peritoneal macrophages J774A.1 lack of endogenous apoE expression were transfected with control and human apoE2, apoE3, and apoE4 isoform‐encoding vectors. Two sets of independently transfected cell lines were studied with similar results obtained. Relative to apoE3 expressing cells, apoE2 and apoE4 expressing macrophages showed significantly higher expression of tumor necrosis factor‐alpha (TNF‐α) mRNA (39%‐51%, p<0.05) and protein (18%‐65%, p<0.05) after lipopolysaccharide (LPS) stimulation. Similarly, relative to apoE3 expressing cells, the expression of interleukin‐6 (IL‐6) mRNA and protein in apoE2 and apoE4 expressing macrophages were significantly higher (63%‐68%, p<0.05) and (54%‐101%, p<0.05) respectively. Interestingly, relative to apoE3 expressing cells, the expression of phosphorylated p38 MAPK, a kinase known to regulate cytokine production, was also significant elevated (33%‐56%, p<0.05) in apoE2 and apoE4 expressing cells under such condition. In conclusion, endogenous expression of apoE modulates macrophage pro‐inflammatory cytokines TNF‐α and IL‐6 expression and p38 MAPK signaling pathway in an isoform‐dependent manner. This work is supported by the Hong Kong Research Grant Council Competitive Earmarked Grant (RGC Reference No. CUHK 4274/02M)