Follistatin-like protein-1 is a novel proinflammatory molecule.
While analyzing gene expression in collagen-induced arthritis, we discovered that a poorly characterized gene, follistatin-like protein 1 (FSTL-1), is highly overexpressed in mouse paws during early arthritis, especially at the interface of synovial pannus and eroding bone. In this study, we show that FSTL-1 is a novel proinflammatory molecule with a previously unrecognized role in inflammation. Transfection of FSTL-1 into macrophages and fibroblasts leads to up-regulation of proinflammatory cytokines, including IL-1beta, TNF-alpha, and IL-6. Overexpression of FSTL-1 in mouse paws by gene transfer results in severe paw swelling and arthritis.
Miyamae
Takako
T
Division of Rheumatology, Children's Hospital of Pittsburgh, School of Medicine, University of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213, USA.
Marinov
Anthony D
AD
Sowders
Dawn
D
Wilson
David C
DC
Devlin
Jason
J
Boudreau
Robert
R
Robbins
Paul
P
Hirsch
Raphael
R
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D038702:Follistatin-Related Proteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D016207:Cytokines; D038702:Follistatin-Related Proteins; C448799:FSTL1 protein, human