title: Extracellular matrix remodeling in Takayasu's arteritis: role of matrix metalloproteinases and adventitial inflammation.
abstract: Takayasu's arteritis (TA) is an inflammatory fibrosing arteritis affecting predominately the aorta and its main branches. Pathogenesis of this disease remains enigmatic. Despite the numerous studies, the role of adventitia in vascular lesion formation in the setting of TA has been ignored. Virtually nothing is known about the mechanism regulating inflammation in the adventitia in the setting of TA. The present study included subjects with Takayasu's arteritis and normal healthy control subjects. Isolated T cells from peripheral blood mononuclear cells (PBMCs) using nylon wool and HUT-78 (human cutaneous T lymphoma cell line) were stimulated with PHA for 24 h. Stimulated cell were fixed with paraformaldehyde and fractionated into membrane, cytosolic and nuclear fractions. These cellular fractions were co-cultured with human fibrosarcoma cell line (HT-1080) and transcriptional expression of matrix metalloproteinases (MMP-1, 3, 9 and TIMP-1) was determined using semiquantitative RT-PCR. Stimulation of MMPs-TIMP synthesis by HT-1080 cells was mimicked by a membranous fraction derived from activated T-cell isolated from TA subjects and activated HUT-78 cells, whereas cytosolic and nuclear fractions were ineffective. In conclusion, for the first time we provide evidence for the presence of a cell surface-specific antigenic moiety on T-cells of TA subjects, which is responsible for activation of fibroblasts (cells predominantly present in adventitia) to enhance MMP production and, therefore, may lead to extracellular matrix degradation.
authors.affiliation: Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
authors.forename: Nitin
authors.initials: N
authors.lastname: Mahajan
authors.forename: Veena
authors.initials: V
authors.lastname: Dhawan
authors.forename: Safrun
authors.initials: S
authors.lastname: Mahmood
authors.forename: Sonal
authors.initials: S
authors.lastname: Malik
authors.forename: Sanjay
authors.initials: S
authors.lastname: Jain
mesh_terms: D000293:Adolescent; D000328:Adult; D063194:Adventitia / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013625:Takayasu Arteritis / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1