A Washington State University research team mapped molecular signals in human tissues and rat data and identified a lesser-known inflammatory route driven by TWEAK and its receptor Fn14. The team found that this TWEAK–Fn14 pathway can join with Tumor Necrosis Factor (TNF) to amplify inflammation, and that when both pathways are active the inflammatory response increases sharply.
Blocking the Fn14 receptor reduced the inflammatory surge that TNF usually causes. Salah-uddin Ahmed, a professor and the corresponding author, described the pathway as a "back-door" entry that lets inflammation continue even when the main TNF route is blocked. The paper's first author is Farheen Shaikh.
The discovery may explain why TNF inhibitors fail for some patients. Rheumatoid arthritis affects roughly 1% of the world, and several TNF inhibitors are FDA approved. The team plans to test therapies that target both pathways together or focus on Fn14 alone.
Difficult words
- molecular — relating to very small chemical structures
- inflammation — body's response to injury or infection with swelling
- pathway — a series of connected biological steps or signalspathways
- receptor — a protein on cells that receives signals
- amplify — to make a signal or effect stronger
- block — to stop or prevent an action or signalBlocking, blocked
- surge — a sudden large increase in amount
- inhibitor — a drug or substance that stops an actioninhibitors
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Discussion questions
- How might this discovery change treatment options for people with rheumatoid arthritis?
- Why could blocking Fn14 help patients who do not respond to TNF inhibitors?
- What benefits or risks do you imagine from therapies that target both pathways together?
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