Differential expression of interleukin-17 family cytokines in intact and complicated human atherosclerotic plaques

• Published in: The Journal of pathology 2010-03, Vol.220 (4), p.499-508
• Main Authors: de Boer, Onno J, van der Meer, Jelger J, Teeling, Peter, van der Loos, Chris M, Idu, Mirza M, van Maldegem, Febe, Aten, Jan, van der Wal, Allard C
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Arteries; Arteriosclerosis; atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - immunology; Biological and medical sciences; Blood and lymphatic vessels; Blotting, Western; Cardiology. Vascular system; Cells, Cultured; Developmental stages; Endothelial cells; Endothelial Cells - immunology; endothelium; Endothelium, Vascular - immunology; Gene Expression - immunology; Helper cells; Humans; IL-17; IL-25; Immune response (humoral); Immunohistochemistry; inflammation; Inflammation Mediators - metabolism; Interleukin 17; Interleukin-17 - biosynthesis; Interleukin-17 - genetics; Investigative techniques, diagnostic techniques (general aspects); Leukocytes (neutrophilic); Lymphocytes B; Lymphocytes T; Mast cells; Medical sciences; Middle Aged; Muscle, Smooth, Vascular - immunology; neutrophils; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Plaques; Plasma Cells - immunology; Receptors, Interleukin - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - genetics; rtPCR; Smooth muscle; TH17; Western blotting
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.2667

In addition to the classical TH1 and TH2 cytokines, members of the recently identified IL-17 cytokine family play an important role in regulating cellular and humoral immune responses. At present nothing is known about the role of these cytokines in atherosclerosis. Expression of IL-17A, -E and -F was investigated in atherosclerotic tissue by rtPCR and immunohistochemistry. IL-17E and its receptor were further studied in cultured smooth muscle cells and endothelial cells, using rtPCR and western blot. rtPCR showed that IL-17A, -E and -F were expressed in the majority of plaques under investigation. IL-17A/F was expressed by mast cells in all stages of plaque development. IL-17A/F⁺ neutrophils were always observed in complicated plaques, but hardly in intact lesions. IL-17A/F⁺ Tcells ('TH17') were never observed. IL-17E was expressed by smooth muscle cells and endothelial cells in both normal and atherosclerotic arteries, and in advanced plaques also extensively by mature B cells. Cultured smooth muscle cells and endothelial cells were found to express both IL-17E and its functional receptor (IL-17RB). The constitutive expression of IL-17E by resident plaque cells, and the additional presence of IL-17E⁺ B cells and IL-17A/F⁺ neutrophils in advanced and complicated plaques indicates a complex contribution of IL-17 family cytokines in human atherosclerosis, depending on the stage and activity of the disease. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.