University of Surrey Researchers Discover Molecular Switch Linking iNOS Protein to Chronic Inflammatory Diseases

Surrey and Oxford researchers identify a molecular switch involving iNOS and IRG1 proteins that could transform treatments for arthritis and heart disease.

By: AXL Media

Published: Apr 25, 2026, 6:41 AM EDT

Source: Information for this report was sourced from EurekAlert!

The Identification of a New Molecular Inflammatory Switch

Researchers from the University of Surrey and the University of Oxford have uncovered a significant biological mechanism that may redefine the treatment of chronic inflammatory conditions. The study focuses on inducible nitric oxide synthase, known as iNOS, a protein long recognized for driving inflammation through the production of nitric oxide. However, this new research demonstrates that iNOS possesses a second, physical role within the cell that is entirely independent of its chemical output. By identifying this "switch," scientists believe they have found a way to influence conditions where the immune system causes tissue damage, such as in cardiovascular disease and arthritis.

The Physical Interaction Between iNOS and IRG1 Proteins

The core of the discovery lies in the direct physical binding between iNOS and another protein called IRG1 located inside the mitochondria. This interaction serves a specific purpose: when iNOS binds to IRG1, it prevents the latter from producing itaconate, a metabolite that normally functions as a natural brake to dampen inflammation. By blocking the production of itaconate, iNOS effectively allows the inflammatory response to continue unchecked. According to the study, this physical coupling challenges the longstanding immunological assumption that iNOS only influences immune behavior via the production of nitric oxide gas.

The Role of BH4 in Determining Cellular Protein Shape

The research highlights that the ability of iNOS to suppress the immune system's natural brakes depends on its physical structure rather than its enzymatic activity. This shape is stabilized by a cofactor known as tetrahydrobiopterin, or BH4. Experimental data showed that even when iNOS was mutated so that it could not produce any nitric oxide, it still suppressed IRG1 as long as it maintained the correct shape determined by BH4. This finding suggests that the structural integrity of the protein is the primary driver of the interaction, opening a new frontier for drug developers who have historically focused on inhibiting what the protein produces rather than how it is shaped.