Nature Immunology study demonstrates that the molecule activates an autocrine loop that sustains expression of inflammation genes but delays that of interferon-response genes.

Investigators at Hospital for Special Surgery identified a mechanism involved in the pathogenesis of inflammatory diseases such as rheumatoid arthritis. 

While much is known about early signaling pathways activated by TNF, little is known about delayed and chronic TNF responses, according to the researchers. In studies using human blood cells and mice, the scientists examined macrophage responses during a two-day period after being stimulated with TNF.

They found that macrophages secreted TNF, which in turn activated surface receptors on the macrophages themselves, spurring the cells into a low and sustained production of a protein called interferon-beta. This protein acted synergistically with TNF signals to induce sustained expression of genes encoding inflammatory molecules and delayed expression of genes encoding interferon-response molecules. Experiments also revealed that this autocrine loop was dependent on the interferon-response factor 1.

“The striking thing about many of these genes that came to our attention first was that there were these classic interferon-response genes that 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. “What we have described is that TNF has both pathogenic affects. It helps to sustain some of these inflammatory chemokines but it also has a potential protective effect, because some of these interferon responses limit the amount of cell proliferation and can also help to limit inflammation.”

The study appeared online on March 16 in Nature Immunology.

Previous articleQ Therapeutics Selects Goodwin to Manufacture Purification mAb
Next articleCorcept to Reap $25.3M from Private Equity Financing