In Johns Hopkins cell experiments, human resistin first primed the NLRP3 inflammasome through HMGB1, then activated it by binding BTK. Hypoxia-exposed mice and autopsy lung tissue from nine women with pulmonary hypertension supplied additional evidence. An anti-resistin antibody weakened the pathway in the laboratory, but the study neither proved the cause of disease nor tested a treatment in patients.
In macrophage experiments, human resistin drove the NLRP3 protein complex, which controls part of the cell's inflammatory response, through two routes. It first increased the production and release of HMGB1, priming the complex. Resistin then bound an enzyme called BTK; BTK's phosphorylation of NLRP3 helped the complex assemble and activate. The chain ultimately increased caspase-1 activity and the release of the inflammatory molecules IL-1β and IL-18.[2]
Alongside the cultured cells, the researchers examined lungs from hypoxia-exposed mice and autopsy lung tissue from nine women aged 50 to 77 with pulmonary hypertension. In the human samples, resistin, BTK and NLRP3 colocalized in the same macrophages. That observation links the pathway to diseased tissue; it does not show that resistin causes pulmonary hypertension or that the finding carries to other inflammatory diseases.[1], [2]
A human monoclonal antibody against resistin reduced NLRP3 pathway activity and inflammatory-molecule release under experimental conditions. The result makes resistin, near the top of this chain, a possible research target. But the study included no patient trial, so the antibody's safety or effectiveness in people was not measured. The nine autopsy samples likewise showed only colocalization in diseased tissue, not a treatment effect.[1], [2]
