TNF Response May Hold Key for Rheumatoid Arthritis
Posted Apr 05 2010 7:00am
Tumor necrosis factor (TNF) has been identified as having a key responsibility in many inflammatory diseases, including rheumatoid arthritis (RA). There has been substantial research into the early signaling pathways activated by TNF, but there is not much known about the delayed and chronic TNF responses.
In addition, cells called macrophages (cells within the tissues that originate from specific white blood cells) produce TNF, but the effect of TNF on the macrophages themselves is not understood.
But a study published March 16th in the online journal Nature Immunology, researchers disclose the discovery of a new mechanism involved in the development of inflammatory diseases. This new mechanism may also provide insight into problems in gene therapy experiments that use adenoviruses to deliver genes to humans.
This study utilized human blood and mice to assess macrophages responses for 2 days after being stimulated with TNF. The researchers found that macrophages secreted TNF and then the TNF activated surface receptors on the macrophages themselves which caused the cells into a low, continued production of the protein interferon-beta.
The interferon-beta acted with TNF signals to induce sustained production of genes encoding inflammatory molecules and delayed production of genes encoding interferon-response molecules.
“The striking thing about many of these genes that came to our attention first was that there were these classic interferon response genes which had previously not been associated with TNF,” said Lionel Ivashkiv, M.D., director of Basic Research at Hospital for Special Surgery, who led the study. “It suggests a new mechanism by which TNF can drive and sustain inflammation.”
According to Dr. Ivashkiv’s team, the results of this, and related studies, may lead to development of new treatments for preventing bone destruction that is linked with some diseases. “So, what it does is sets up the next series of studies, in animal models, to try to determine whether this induction of interferon is beneficial or not.”