title: Mediators of inflammation are down-regulated while apoptosis is up-regulated in rheumatoid arthritis synovial tissue by polymerized collagen.
abstract: The aim of the study was to determine whether collagen-polyvinylpyrrolidone (collagen-PVP) modifies some proinflammatory responses in synovium cultures from rheumatoid arthritis (RA) patients. Synovium from 10 RA patients were cultured with or without 1% collagen-PVP. Tissues on the 3rd, 5th and 7th culture day were sectioned and stained by the Herovici technique. Total collagen and type I/III collagen ratios were evaluated by the Woessner micromethod and by interrupted gel electrophoresis, respectively. Collagenolytic activity was assessed by degradation of [3H]-collagen in supernatants. TIMP-1, IL-1beta and TNF-alpha were determined in supernatants by ELISA, and the results were normalized by DNA concentration. IL-1beta, TNF-alpha, IL-6, IL-8, MMP-1, TIMP-1, Cox-1, VCAM-1, ICAM-1 and Fas/APO95 expression was evaluated by immunohistochemistry. Apoptosis was detected by TUNEL technique. The histological analysis and electrophoresis revealed a 1.7-fold increase of type III collagen in a time-dependent fashion in collagen-PVP-treated cultures. Proinflammatory cytokines (IL-1beta: 58 +/- 9 versus 22 +/- 10; TNF-alpha: 41 +/- 6 versus 11 +/- 3; IL-8: 59 +/- 12 versus 29 +/- 9; treated versus untreated), adhesion molecule (ICAM-1: 57 +/- 11 versus 29 +/- 15; VCAM-1: 49 +/- 7 versus 21 +/- 13; treated versus untreated) as well as Cox-1 (59 +/- 10 versus 20 +/- 3) expression was down-regulated in RA synovium treated. Meanwhile, TIMP-1 (36 +/- 7 versus 57 +/- 11) and Fas expression (20 +/- 10 versus 55 +/- 13) and apoptosis (14 +/- 3 versus 55 +/- 5) were up-regulated in treated cultures compared with controls. In supernatants, the collagenolytic activity, as well as IL-1beta and TNF-alpha, levels were all down-regulated in treated cultures (two, three, fourfold, respectively). The addition of collagen-PVP to synovium-induced down-modulation of some inflammatory parameters and an increase in apoptosis of synovial cells. Perhaps this mechanism could contribute to inhibit outgrowth of pannus formation and to down-regulate inflammation of joints in patients with RA.
authors.affiliation: Department of Cellular Biology, Instituto de Investigaciones Biomédicas, UNAM, Mexico City, Mexico. furuzawa@servidor.unam.mx
authors.forename: J
authors.initials: J
authors.lastname: Furuzawa-Carballeda
authors.forename: R
authors.initials: R
authors.lastname: Rodríquez-Calderón
authors.forename: L
authors.initials: L
authors.lastname: Díaz de León
authors.forename: J
authors.initials: J
authors.lastname: Alcocer-Varela
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D001327:Autoimmune Diseases / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D003094:Collagen / Q000494:pharmacology*; D051545:Cyclooxygenase 1; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D053222:Fas Ligand Protein; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins; D008875:Middle Aged; D009924:Organ Culture Techniques; D011205:Povidone / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D018836:Inflammation Mediators; D007378:Interleukins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; C120488:collagen-PVP; D019014:fas Receptor; D003094:Collagen; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D020781:Matrix Metalloproteinase 1; D011205:Povidone