1: Ectopic upregulation of membrane-bound IL6R drives vascular remodeling in pulmonary arterial hypertension.
Science of the Month - August 2018
This study summarizes the results of work by Yuichi Tamura (83rd graduate), currently an associate professor at the International University of Health and Welfare School of Medicine, conducted while he was studying abroad at the French National Center for Pulmonary Hypertension, University of Paris.
Pulmonary arterial hypertension is designated as an intractable disease by the Ministry of Health, Labour and Welfare, affecting several thousand patients nationwide. It is caused by remodeling, primarily involving vascular endothelial cell damage and smooth muscle proliferation in the peripheral pulmonary arteries, but the detailed mechanism has not been clarified. It was known that inflammatory cytokines, including IL-6, are elevated in the serum of patients with pulmonary arterial hypertension and are poor prognostic factors, but it was unclear how they act on the pulmonary blood vessels themselves. Dr. Tamura was the first to reveal that in patients with pulmonary arterial hypertension, the membrane-bound IL-6 receptor is highly expressed in pulmonary artery smooth muscle cells, and that the IL-6 signal contributes to pulmonary artery remodeling by conferring anti-apoptotic resistance to these cells. Furthermore, by carefully demonstrating that blocking the IL-6 receptor improves pulmonary hypertension using models such as a rat model of pulmonary hypertension and a smooth muscle-specific IL-6 receptor knockout mouse model, this report provides high-quality translational research that offers a scientific basis for future treatment of pulmonary hypertension with IL-6 receptor antibodies, which are scheduled for clinical trials.
(Yuichi Tamura, 83rd graduate, currently Associate Professor, International University of Health and Welfare School of Medicine)