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.
Proapoptotic Bcl-2 family member Bim is particularly relevant for deletion of autoreactive and activated T and B cells, implicating Bim in autoimmunity.
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.
Although its genetic variants are reported to be involved in cancers and autoimmune diseases, little information is available regarding BCL2 polymorphisms in male spermatogenesis.
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.
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.
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 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.
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.
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).
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.