Placenta Protein May Lead to Rheumatoid Arthritis Treatment
Posted Mar 06 2009 2:54pm
Researchers are not sure of the exact causes of rheumatoid arthritis (RA), but they have discovered that cytokines (bioactive proteins), in particular TNF-alpha and IL-6 are significant contributors. These cytokines cause inflammation which leads to destruction of the joints and tissues.
The action of another cytokine, placenta growth factor (PIGF), is suspected to be critical for the formation of new blood vessels in the placenta necessary to deliver adequate oxygen and nutrients to fetus. A new study led by Wan-Uk Kim of Catholic University of Korea in Seoul, Korea, examined the impacts of PIGF on the inflammatory process of RA. The results of the study suggest that PIGF may have an important role in inflammation in joints with rheumatoid arthritis.
The researchers analyzed blood and synovial fluid cells from RA patients and from healthy controls. They discovered that the key source of PIGF production in RA patients is the synovial cells and that PIGF stimulates TNF-alpha and IL-6 production. They also found that the increases in TNF-alpha and IL-6 production induced by PIGF might be caused by high levels of a PIGF receptor, know as flt-1, which is linked to the inflammatory response of RA patients. Additionally, the researchers identified a new peptide to inhibit PIGF action. Injecting this peptide into arthritic mice resulted in reduced severity of arthritis and prevention of the arthritis progression. They also determined that eliminating the PIGF gene in mice prevented the development of antibody-induced arthritis.
The peptide they identified inhibits binding of PIGF to the flt-1 receptor and could be clinically valuable because it is easily synthesized and does not elicit unwanted immune response.
According to the report authors, “These findings provide new insight into the pathogenic mechanism of RA and emphasize the importance of PIGF and flt-1 as potential candidates for therapy, in addition to their being a common cue of angiogenesis and the inflammatory process.”
The researchers are currently conducting research to improve the activity of the anti-flt-1 peptide by modifying its length and structure.