PMID: 19918315Nov 18, 2009Paper

Sex hormones and leflunomide treatment of human macrophage cultures: effects on apoptosis.

International Journal of Clinical and Experimental Medicine
P MontagnaM Cutolo

Abstract

In order to establish the possible gender influence on the activity of leflunomide (LEF) in rheumatoid arthritis (RA), we evaluated the proapoptotic activity of the active LEF metabolite A77 1726 (LEF-M), in combination with sex hormones, on cultures of human macrophages. In particular, we focussed our investigation on the triggering phase of the apoptosis. Cultures of macrophages from activated THP-1 cells and from RA synovial tissues were treated with LEF-M alone [30muM] or in presence of 17beta-estradiol (E2) (10(-9)M) or testosterone (T) (10-(8)M) for 24 hours. FAS, FAS-L, FADD (Fas-Associated via Death Domain) and FLICE (FADD-Like Interleukin-1 beta Converting Enzyme) were evaluated by immunocytochemistry (ICC), Western blot (WB) and reverse transcriptase-multiplex polymerase chain reaction (RT-MPCR). Regarding macrophages from THP-1 cells (M), the ICC showed that LEF-M exerted a significant up-regulation on all investigated apoptotic proteins, when compared to untreated cells (control) (p<0.001). On the contrary, E2 significantly increased FAS-L positivity (p<0.05) and down-regulated FADD (p<0.01), while others apoptotic proteins were not modulated when compared to control. Regarding RA synovial macrophages (SM), the ICC ...Continue Reading

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis