The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Tnfaip6  -  tumor necrosis factor alpha induced protein 6

Mus musculus

Synonyms: TNF alpha-induced protein 6, TNF-stimulated gene 6 protein, TSG-6, Tnfip6, Tsg6, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Tnfaip6

  • Thioglycollate-induced sterile peritonitis was also assessed, to monitor the early events of neutrophil extravasation in wild-type and Tnfip6-deficient mice in the presence or absence of treatment with recombinant murine Tnfip6 [1].
  • Loss of control over several components of inflammation resulted in extensive and rapid cartilage degradation, bone erosion, joint ankylosis, and deformities in Tnfip6-null animals [1].
  • Tumor necrosis factor stimulated gene-6 (TSG-6) has been previously shown to be induced in vitro in several cell types by proinflammatory cytokines, and in vivo in pathological conditions such as rheumatoid arthritis [2].
  • METHODS: To determine the effect of TSG-6 on chronic inflammatory joint disease, we induced CIA in DBA/1J mice by immunization with bovine type II collagen [3].

High impact information on Tnfaip6

  • Tumor necrosis factor-induced protein-6 (TNFIP6 or TSG6) has been shown to be specifically expressed during this process [4].
  • Recombinant TNFIP6 is able to catalyze the covalent transfer of heavy chains to hyaluronan in a cell-free system, restore the expansion of Tnfip6-null cumulus cell-oocyte complexes in vitro, and rescue the fertility in Tnfip6-null females [4].
  • In addition to immobilized hyaluronan, full-length TSG-6 also binds free hyaluronan and all chondroitin sulfate isoforms under physiological conditions [5].
  • TSG-6 protein, up-regulated in inflammatory lesions and in the ovary during ovulation, shows anti-inflammatory activity and plays an essential role in female fertility [5].
  • TSG-6 protein binding to glycosaminoglycans: formation of stable complexes with hyaluronan and binding to chondroitin sulfates [5].

Biological context of Tnfaip6


Anatomical context of Tnfaip6


Associations of Tnfaip6 with chemical compounds

  • These observations identify TSG-6 as a target of PG action and show that its production in ovulatory follicles is associated with proper formation of the cumulus-derived extracellular matrix [9].
  • FSH but not PGE2 rescued expansion and production of TSG-6 in the EP2 null COCs, indicating that generation of a cAMP signal is essential [10].
  • The TSG-6/IalphaI complex then blocks serine proteases, including the plasminogen-plasmin activation, probably the most important component in the activation processes of matrix metalloproteinases [11].
  • Although overexpression of TSG-6 inhibited invasion of androgen-independent cells (P = 0.007), antisense TSG-6 reversed this effect [12].

Regulatory relationships of Tnfaip6

  • OBJECTIVE: To gain insight into the mechanisms of the antiinflammatory effect of tumor necrosis factor alpha (TNFalpha)-induced protein 6 (Tnfip6) in arthritis, using Tnfip6-deficient animals [1].
  • We document that TSG-6 message and protein are induced by cAMP/protein kinase A/MAPK signaling pathways and that blocking these cascades prevents expansion and the production of TSG-6 [10].

Other interactions of Tnfaip6

  • CONCLUSION: Tnfip6 is a multifunctional antiinflammatory protein that is produced at the site of inflammation and can be retained by the hyaluronan-rich extracellular matrix [1].
  • Whereas Tnfip6 is induced in all granulosa cells by the LH surge, Ptx3 expression in the ovary is specifically observed after the LH surge in the cumulus granulosa cells adjacent to the oocyte [13].
  • Animals treated with recombinant TSG-6 developed significantly reduced levels of IgG1, IgG2a, and IgG2b antibodies against bovine and murine type II collagen [3].
  • Mice null for COX-2 and EP2 fail to ovulate and exhibit impaired COC expression of TSG-6 [14].

Analytical, diagnostic and therapeutic context of Tnfaip6

  • In support of the antiinflammatory effect of Tnfip6 via the inhibition of polymorphonuclear (PMN) cell efflux, neutrophil invasion during thioglycollate-induced peritonitis was 2-fold higher in Tnfip6-deficient animals than in wild-type animals, but was dramatically suppressed by intravenous injection of recombinant murine Tnfip6 [1].
  • OBJECTIVE: To examine the effect of recombinant TSG-6 on collagen-induced arthritis (CIA) in DBA/1J mice [3].
  • Intraarticular injection of mBSA uniformly induced severe inflammation both in control (wild-type and an irrelevant transgenic line) mice and in tsg6/tnfip6 transgenic mice [15].
  • Immunohistochemistry of the human prostate tumor array showed a decrease in TSG-6-positive cells with increasing grade relative to normal prostate (P = 0.0001) [12].
  • We have also identified TSG-6 as a potential marker that could be used for early diagnosis and prognosis of cancerous or precancerous lesions [12].


  1. Enhanced neutrophil extravasation and rapid progression of proteoglycan-induced arthritis in TSG-6-knockout mice. Szántó, S., Bárdos, T., Gál, I., Glant, T.T., Mikecz, K. Arthritis Rheum. (2004) [Pubmed]
  2. Coding sequence, exon-intron structure and chromosomal localization of murine TNF-stimulated gene 6 that is specifically expressed by expanding cumulus cell-oocyte complexes. Fülöp, C., Kamath, R.V., Li, Y., Otto, J.M., Salustri, A., Olsen, B.R., Glant, T.T., Hascall, V.C. Gene (1997) [Pubmed]
  3. Amelioration of collagen-induced arthritis in DBA/1J mice by recombinant TSG-6, a tumor necrosis factor/interleukin-1-inducible protein. Mindrescu, C., Thorbecke, G.J., Klein, M.J., Vilcek, J., Wisniewski, H.G. Arthritis Rheum. (2000) [Pubmed]
  4. Impaired cumulus mucification and female sterility in tumor necrosis factor-induced protein-6 deficient mice. Fülöp, C., Szántó, S., Mukhopadhyay, D., Bárdos, T., Kamath, R.V., Rugg, M.S., Day, A.J., Salustri, A., Hascall, V.C., Glant, T.T., Mikecz, K. Development (2003) [Pubmed]
  5. TSG-6 protein binding to glycosaminoglycans: formation of stable complexes with hyaluronan and binding to chondroitin sulfates. Wisniewski, H.G., Snitkin, E.S., Mindrescu, C., Sweet, M.H., Vilcek, J. J. Biol. Chem. (2005) [Pubmed]
  6. Reduced susceptibility to collagen-induced arthritis in DBA/1J mice expressing the TSG-6 transgene. Mindrescu, C., Dias, A.A., Olszewski, R.J., Klein, M.J., Reis, L.F., Wisniewski, H.G. Arthritis Rheum. (2002) [Pubmed]
  7. The preantral granulosa cell to cumulus cell transition in the mouse ovary: Development of competence to undergo expansion. Diaz, F.J., O'brien, M.J., Wigglesworth, K., Eppig, J.J. Dev. Biol. (2006) [Pubmed]
  8. Hyaluronan binding properties of a CD44 chimera containing the link module of TSG-6. Lesley, J., English, N.M., Gál, I., Mikecz, K., Day, A.J., Hyman, R. J. Biol. Chem. (2002) [Pubmed]
  9. Decreased expression of tumor necrosis factor-alpha-stimulated gene 6 in cumulus cells of the cyclooxygenase-2 and EP2 null mice. Ochsner, S.A., Russell, D.L., Day, A.J., Breyer, R.M., Richards, J.S. Endocrinology (2003) [Pubmed]
  10. Disrupted function of tumor necrosis factor-alpha-stimulated gene 6 blocks cumulus cell-oocyte complex expansion. Ochsner, S.A., Day, A.J., Rugg, M.S., Breyer, R.M., Gomer, R.H., Richards, J.S. Endocrinology (2003) [Pubmed]
  11. Anti-inflammatory and chondroprotective effect of TSG-6 (tumor necrosis factor-alpha-stimulated gene-6) in murine models of experimental arthritis. Bárdos, T., Kamath, R.V., Mikecz, K., Glant, T.T. Am. J. Pathol. (2001) [Pubmed]
  12. 2-Methoxyestradiol inhibits prostate tumor development in transgenic adenocarcinoma of mouse prostate: role of tumor necrosis factor-alpha-stimulated gene 6. Garcia, G.E., Wisniewski, H.G., Lucia, M.S., Arevalo, N., Slaga, T.J., Kraft, S.L., Strange, R., Kumar, A.P. Clin. Cancer Res. (2006) [Pubmed]
  13. Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility. Varani, S., Elvin, J.A., Yan, C., DeMayo, J., DeMayo, F.J., Horton, H.F., Byrne, M.C., Matzuk, M.M. Mol. Endocrinol. (2002) [Pubmed]
  14. Ovulation: new factors that prepare the oocyte for fertilization. Richards, J.S. Mol. Cell. Endocrinol. (2005) [Pubmed]
  15. Cartilage-specific constitutive expression of TSG-6 protein (product of tumor necrosis factor alpha-stimulated gene 6) provides a chondroprotective, but not antiinflammatory, effect in antigen-induced arthritis. Glant, T.T., Kamath, R.V., Bárdos, T., Gál, I., Szántó, S., Murad, Y.M., Sandy, J.D., Mort, J.S., Roughley, P.J., Mikecz, K. Arthritis Rheum. (2002) [Pubmed]
WikiGenes - Universities