Collagen Disease Increased Models

One of the most unusual mechanisms claimed for milk thistle involves an increase in RNA polymerase I activity in nonmalignant hepatocytes but not in hepatoma or other malignant cell lines. By increasing this enzyme s activity, enhanced protein synthesis and cellular regeneration may occur in diseased but not malignant cells. Milk thistle may have a role in hepatic fibrosis. In an animal model of cirrhosis, it reduced collagen accumulation, and in an in vitro model it reduced expression of the profibrogenic cytokine TGF-13. 

MAPKAP kinase 2 (MK2) plays a key role in the production of pro-inflammatory cytokines such as TNF-a. MK2 is activated by the mitogen-activated protein (MAP) kinase p38 [1-3]. Activated MK2 phosphorylates a number of target proteins in immune cells resulting in cytokine production and cellular proliferation and activation. Mice lacking MK2 are healthy and fertile, but they fail to increase production of pro-inflammatory cytokines such as TNF-a, lL-6, and IFN-y [4] in response to stimuli such as lipopolysaccharide. MK2 knockout mice are resistant to the development of collagen-induced arthritis, a model for human rheumatoid arthritis [5]. The catalytic activity of MK2 is required to mount the pro-inflammatory response [6]. These and related studies have attracted attention to MK2 as a target for the design of therapeutic treatments for rheumatoid arthritis and other TNF-a-driven diseases. 

---