title: Identification of a specific haptoglobin C-terminal fragment in arthritic synovial fluid and its effect on interleukin-6 expression.
abstract: Haptoglobin (Hp), a major acute-phase plasma protein, has been found in arthritic synovial fluid (SF). However, the function and structural modifications of Hp in arthritic SF are unknown. To investigate in vivo generation of modified Hp associated with inflammatory disease, we examined a new Hp isoform in SF from patients with rheumatoid arthritis (RA). Specific Hp fragments of 28 000 and 15 000 molecular weight were identified in SF of patients with RA, and the two polypeptides were presumed to be fragments of the Hp β-chain (43 000 MW) produced by cleavage with plasmin. The 15 000 MW fragment, which is a C-terminal region of Hp, was observed at higher frequency and levels in RA than in osteoarthritis. Plasmin activity was also higher in SF of RA patients. A recombinant 15 000 MW Hp fragment up-regulated interlukin-6 expression in monocytic cells. These findings indicate that the C-terminal Hp fragment is generated by plasmin in local inflammatory environments and acts as an inflammatory mediator. They further suggest that a specific Hp fragment might be applied as a novel biomarker for the diagnosis and prognosis of inflammatory diseases such as RA.
authors.affiliation: Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Park
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Oh
authors.forename: Nam-Hoon
authors.initials: NH
authors.lastname: Kim
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.forename: In-Sook
authors.initials: IS
authors.lastname: Kim
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D005341:Fibrinolysin / Q000378:metabolism; D006242:Haptoglobins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000737:chemistry / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008970:Molecular Weight; D009000:Monocytes / Q000378:metabolism; D010003:Osteoarthritis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C485359:HP protein, human; D006242:Haptoglobins; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D010446:Peptide Fragments; D005341:Fibrinolysin
keywords: biomarker; haptoglobin; plasmin; rheumatoid arthritis; synovial fluid