title: Effect of a derivatized tetrapeptide from lactoferrin on nitric oxide mediated matrix metalloproteinase-2 production by synovial fibroblasts in collagen-induced arthritis in rats.
abstract: Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent proteolytic enzymes, which degrade several components of extracellular matrix, in arthritic synovial cells. In cultured synovial fibroblasts, both nitric oxide (NO) and reactive oxygen species (ROS) are potent inducers of MMPs production. PEP1261, a tetrapeptide derivative used in this study, corresponds to residues of 39-42 human lactoferrin. The parent protein lactoferrin is able to inhibit the production of free radicals in rheumatoid joints and it regulates many aspects of inflammation. This study is aimed to examine the effects of PEP1261 on MMP-2 production in the presence of nitric oxide donor in cultured synovial fibroblasts from collagen-induced arthritic rats. PEP1261 affects a significant reduction in nitrite levels as well as in MMP-2 production in SNAP stimulated synovial fibroblasts and this is validated by gelatin zymography and immunoblot analysis. Furthermore, RTPCR analysis has demonstrated that PEP1261 inhibits MMP-2 mRNA expression in SNAP treated synovial fibroblasts. The results of this study suggest that PEP1261 possesses antiarthritic activity by inhibiting nitrite levels as well as MMP-2 expression better than control peptides viz., KRDS and RGDS.
authors.affiliation: Department of Biotechnology, Central Leather Research Institute, Chennai 600020, India.
authors.forename: Dilly Ashok
authors.initials: DA
authors.lastname: Kumar
authors.forename: Kalidindi V S Narayana
authors.initials: KV
authors.lastname: Raju
authors.forename: K
authors.initials: K
authors.lastname: Settu
authors.forename: K
authors.initials: K
authors.lastname: Kumanan
authors.forename: Rengarajulu
authors.initials: R
authors.lastname: Puvanakrishnan
mesh_terms: D000818:Animals; D001168:Arthritis / Q000378:metabolism*; D003094:Collagen / Q000737:chemistry*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D007781:Lactoferrin / Q000737:chemistry* / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D009569:Nitric Oxide / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry; D012313:RNA / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013583:Synovial Membrane / Q000378:metabolism*
chemical_list: C402764:Boc-Lys(Boc)-Arg-Asp-Ser(tBu)-OtBu; D010446:Peptide Fragments; D010455:Peptides; D009569:Nitric Oxide; D012313:RNA; D003094:Collagen; D007781:Lactoferrin; D020778:Matrix Metalloproteinase 2