Experimental models of arthritis in which pathogenesis is dependent on TNF expression

M. S. Drutskaya, G. A. Efimov, R. V. Zvartsev, A. A. Chashchina, D. M. Chudakov, S. V. Tillib, A. A. Kruglov, S. A. Nedospasov

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by joint damage as well as systemic manifestations. The exact cause of RA is not known. Both genetic and environmental factors are believed to contribute to the development of this disease. Increased expression of tumor necrosis factor (TNF) has been implicated in the pathogenesis of RA. Currently, the use of anti-TNF drugs is one of the most effective strategies for the treatment of RA, although therapeutic response is not observed in all patients. Furthermore, due to non-redundant protective functions of TNF, systemic anti-TNF therapy is often associated with unwanted side effects such as increased frequency of infectious diseases. Development of experimental models of arthritis in mice is necessary for studies on the mechanisms of pathogenesis of this disease and can be useful for comparative evaluation of various anti-TNF drugs. Here we provide an overview of the field and present our own data with two experimental models of autoimmune arthritis - collagen-induced arthritis and antibody-induced arthritis in C57Bl/6 and BALB/c mice, as well as in tnf-humanized mice generated on C57Bl/6 back-ground. We show that TNF-deficient mice are resistant to the development of collagen-induced arthritis, and the use of anti-TNF therapy significantly reduces the disease symptoms. We also generated and evaluated a fluorescent detector of TNF overexpression in vivo. Overall, we have developed an experimental platform for studying the mechanisms of action of existing and newly developed anti-TNF drugs for the treatment of rheumatoid arthritis.

Original languageEnglish
Pages (from-to)1349-1357
Number of pages9
JournalBiochemistry (Moscow)
Volume79
Issue number12
DOIs
Publication statusPublished - Dec 2014
Externally publishedYes

Keywords

  • anti-cytokine therapy
  • autoimmune diseases
  • rheumatoid arthritis
  • tumor necrosis factor

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