Follistatin-Like Protein-1 Is a Novel Proinflammatory Molecule1

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-1β, TNF-α, and IL-6. Overexpression of FSTL-1 in mouse paws by gene transfer results in severe paw swelling and arthritis.

[1]  Norbert Gretz,et al.  Identification of metastasis-associated genes in prostate cancer by genetic profiling of human prostate cancer cell lines. , 2005, Anticancer research.

[2]  K. Tokunaga,et al.  Follistatin-related protein gene (FRP) is expressed in the synovial tissues of rheumatoid arthritis, but its polymorphisms are not associated with genetic susceptibility. , 2004, Clinical and experimental rheumatology.

[3]  K. Nose,et al.  Structural Characterization of TSC-36/Flik , 2004, Journal of Biological Chemistry.

[4]  T. Mimori,et al.  Ameliorative effects of follistatin-related protein/TSC-36/FSTL1 on joint inflammation in a mouse model of arthritis. , 2004, Arthritis and rheumatism.

[5]  B. Decallonne,et al.  The use of real-time reverse transcriptase PCR for the quantification of cytokine gene expression. , 2003, Journal of biomolecular techniques : JBT.

[6]  T. Mimori,et al.  Potential preventive effects of follistatin-related protein/TSC-36 on joint destruction and antagonistic modulation of its autoantibodies in rheumatoid arthritis. , 2003, International immunology.

[7]  B. Aronow,et al.  DNA microarray analysis reveals novel gene expression profiles in collagen-induced arthritis. , 2002, Clinical immunology.

[8]  I. Sargent,et al.  Effect of cytokines and growth factors on the secretion of inhibin A, activin A and follistatin by term placental villous trophoblasts in culture. , 2001, European journal of endocrinology.

[9]  J. Vass,et al.  Regulation of a multigenic invasion programme by the transcription factor, AP-1: re-expression of a down-regulated gene, TSC-36, inhibits invasion , 2000, Oncogene.

[10]  K. Tsuchida,et al.  Expression of a TGF-β1 inducible gene, TSC-36, causes growth inhibition in human lung cancer cell lines , 2000 .

[11]  K. Nose,et al.  cDNA cloning and distribution of the Xenopus follistatin-related protein. , 1999, Biochemical and biophysical research communications.

[12]  K. Mori,et al.  Cloning of follistatin-related protein as a novel autoantigen in systemic rheumatic diseases. , 1998, International immunology.

[13]  Shao,et al.  Suppression of IL‐6 biological activities by activin A and implications for inflammatory arthropathies , 1998, Clinical and experimental immunology.

[14]  A. Yoshiki,et al.  TSC-36 (Follistatin-Related Polypeptide) Gene Expression in Estrogen Receptor Positive Osteoblastic Cell Line, CDO7F , 1997, Calcified Tissue International.

[15]  M. Kitamura,et al.  Construction of adenovirus vectors through Cre-lox recombination , 1997, Journal of virology.

[16]  K. Nose,et al.  Decrease in the expression of a novel TGF beta1-inducible and ras-recision gene, TSC-36, in human cancer cells. , 1997, Cancer letters.

[17]  E. Giannini,et al.  Induction of T helper cell hyporesponsiveness in an experimental model of autoimmunity by using nonmitogenic anti-CD3 monoclonal antibody. , 1994, Journal of immunology.

[18]  K. Nose,et al.  Cloning from a mouse osteoblastic cell line of a set of transforming-growth-factor-beta 1-regulated genes, one of which seems to encode a follistatin-related polypeptide. , 1993, European journal of biochemistry.