Universal Journal of Medical Science Vol. 1(2), pp. 50 - 55
DOI: 10.13189/ujmsj.2013.010205
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Induction of Rheumatoid Arthritis and Response to Tyrosine Kinase Inhibitors


Emad Y. Moawad*
Dept. of Engineering, Ain Shams University, Cairo, Egypt

ABSTRACT

The goal of this work is to determine the role of the autoimmune cells in Rheumatoid arthritis (RA) induction and the immunomodulatory mechanism of therapy with Tyrosine Kinase Inhibitors (TKIs) in RA attenuation. B cells were isolated from naive DBA/1 mouse spleens and stimulated for 72 hours with LPS as a positive control forming a mouse model of RA in the presence or absence of 1–5 μM imatinib. B cell staging were assessed by adding 1 μCi of [3H] thymidine for measuring proliferation in the final 18 hours of the stimulation, and a Beta plate scintillation counter was used to quantitate incorporated radioactivity. Samples of C1.MC/57.1 mast cells were stimulated with 100 ng/mL of Self Cell Factor (SCF) as a positive control of a mouse model of RA in the absence or presence of 1-5 μM of imatinib. Tumour Necrotic Factor (TNF) levels in culture supernatants from C1.MC/57.1 mast cells were measured by ELISA. The histologic grade (HG) and the level of TNF of the mouse model of RA were 1/10 and 10 times respectively those in the control one. This inverse proportion clarifies that RA disease is the result of big increase in TNF level perpetuating local inflammation and joint destruction leads to a major decrease in with the same ratio. The addition of 1 and 5 μM doses of imatinib increased by 200% and 300% respectively while decreased TNF level to be 12.5% and 10% respectively of that in the mouse model of RA restoring rate of TNF level of normal tissue. This demonstrates that effective mitigation of symptoms of RA is the result of a significant increase in HG because of the cell cycle arrest resulting from the treatment of TKIs which leads to a significant reduction in the level of TNF but with a different ratio to increase HG unlike happened in incidence of RA.

KEYWORDS
Platelet-derived Growth Factor, Tumour Necrotic Factor, Histologic Grade

Cite this paper
Emad Y. Moawad . "Induction of Rheumatoid Arthritis and Response to Tyrosine Kinase Inhibitors." Universal Journal of Medical Science 1.2 (2013) 50 - 55. doi: 10.13189/ujmsj.2013.010205.