Impaired repairment of immune system and apoptosis regulation can be seen as major landmarks in autoimmune disorders such as the mutation of p53 gene which results in rheumatoid arthritis, bowel disease which consequently lead to tissue destruction, inflammation and dysfunctioning of body organs.
Here we show that clofazimine (Lamprene), a drug already used in the clinic for autoimmune diseases and leprosy, is able to efficiently kill in vitro five different PDAC cell lines harboring p53 mutations.
Some SNPs of TP53, involving a different apoptotic ability of p53, have been associated with increased susceptibility to develop autoimmune diseases as well as cancer.
We also discuss the role of p53 in controlling the balance between Th17 cells and Tregs, the alteration of which is shown to be involved in the development of autoimmunity.
Our results not only reveal a novel mechanism whereby p53 is involved in the posttranscriptional regulation of Cyr61 expression via miRNA-22, but also provide a molecular explanation for the role of somatic mutations of p53, which are frequently observed in RA synovial tissue, in the etiology of this autoimmune disease.
Recent studies have implicated PTPN22 and tp53 in susceptibility to several autoimmune diseases, including rheumatoid arthritis, suggesting that these genes are important in maintaining immune homeostasis.
Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, plays an important role in the process of autoimmune diseases. p53 is related to the regulation of cell growth and prevention of carcinogenesis.
We conclude that ALVAC-p53 can be administered intravenously to colorectal cancer patients without serious toxicity or pathological autoimmunity and can induce immune responses against p53.
Sjögren's syndrome cells express an enhanced G1 checkpoint function which may be mediated partly by p53 phosphorylation, suggesting that an abnormal stress response in SS is of relevance for the development of this autoimmune disease.