Interleukin-6 and interleukin-8 protein and gene expression in human arterial atherosclerotic wall.
Interleukin 6 (IL-6) and interleukin 8 (IL-8) are present in the human arterial atherosclerotic wall as cellular and extracellular deposits in the connective tissue matrix. Quantitative determinations of IL-6 by ELISA showed mean values of 27.6 +/- 3.3 ng/100 mg protein in normal intima, 37.3 +/- 2.1 ng/100 mg protein in fibrous plaque and 25.7 +/- 4.3 ng/100 mg total extracted protein in media. IL-8 levels were 3.5 +/- 0.6 ng/100 mg protein in normal intima, 11.3 +/- 2.1 ng/100 mg protein in fibrous plaque and 8.5 +/- 1.4 ng/100 mg total extracted protein in media. Fibrous plaques presented statistically significant higher levels of both IL-6 and IL-8. IL-6 and IL-8 gene transcripts were present in human iliac fibrous plaque and media prelevated at surgery indicating that a local production by the cells of the arterial wall participate to their accumulation. We also tested the role of complement activation in induction of IL-6 and IL-8 protein synthesis as well as the subsequent activation of endothelial cells. Only IL-8 was induced by complement activation and this may contribute to increased IL-8 levels found in the atherosclerotic wall. When exposed to terminal complement complexes, endothelial cells in culture also showed an increase of both DNA-synthesis and p70 S6 kinase activity indicating that complement is able to induce not only IL-8 synthesis but also cell activation. The presence of IL-6 and IL-8 in the arterial wall where complement activation also occurred, clearly show the involvement of inflammatory events in initiation and progression of atherosclerosis.
Rus
H G
HG
Medical Clinic no. 1, 3-5, Cluj-Napoca, Romania.
Vlaicu
R
R
Niculescu
F
F
D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005263:Femoral Artery / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D015345:Oligonucleotide Probes / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012313:RNA / Q000032:analysis*; D019893:Ribosomal Protein S6 Kinases
D015850:Interleukin-6; D016209:Interleukin-8; D015345:Oligonucleotide Probes; D012313:RNA; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases