Although the occurrence of circulating T lymphocytes with abnormally high bcl-2 expression is not specific for SLE, it is evidence for a dysregulation of lymphocytic programmed cell death in this autoimmune disease.
Since defective apoptosis has been suggested to play a role in the development of autoimmune diseases, we have investigated the expression of the proto-oncogene bcl-2 in patients with rheumatoid arthritis (RA).
The different anti-apoptotic function resulting from the different expression of bcl-2 protein in lymphocytes seems to be associated with the development of autoimmune disease, indicating that the bcl-2 gene affects human autoimmune disease.
The Bcl-2 gene located within this region, is a candidate gene because of its role in apoptosis, a physiological mechanism that could be deregulated in autoimmune disease.
Accumulating evidence has suggested a role for the anti-apoptotic protein BCL2 in the development of autoimmune diseases, including type 1 diabetes mellitus (T1DM).
The purpose of this study was to examine the potential of Bim, an agent that mimics the action of Bcl-2 homology 3 (BH3) domain-only proteins that have shown success in preclinical studies of cancer, in the treatment of autoimmune disease.
This process was only partly dependent on the Bcl-2 pathway, but markedly inefficient in MRL-Fas(lpr) lupus mice, suggesting that defective apoptosis of isotype-switched autoreactive B cells is central to Fas mutation-associated systemic autoimmunity.
Although its genetic variants are reported to be involved in cancers and autoimmune diseases, little information is available regarding BCL2 polymorphisms in male spermatogenesis.
Since the Bcl-2 family of proteins is the key regulator of apoptosis, the abnormalities in its function have been implicated in many diseases including cancer, neurodegenerative disorders, ischemia and autoimmune diseases.
Proapoptotic Bcl-2 family member Bim is particularly relevant for deletion of autoreactive and activated T and B cells, implicating Bim in autoimmunity.
Moreover, MLT inhibits NF-κB signaling pathway to reduce TNF-α and IL-1β expression, promotes Nrf2 gene and protein expression to reduce oxidative and inflammatory states and regulates Bax and Bcl-2 to reduce apoptosis; all of which alleviate the development of autoimmune diseases.