Abstract

Inflammation, a critical aspect of the immune system's defense and recovery processes, manifests in two primary forms: acute and chronic. Understanding and controlling these responses are vital for managing various inflammatory conditions. 2-Hydroxyisocaproic acid is a physiological substance and the 2-hydroxy-analogue of the essential amino acid leucine. This research focuses on the interaction of 2-Hydroxyisocaproic acid with key inflammatory mediators, matrix metalloproteinase 8, and Developmental Endothelial Locus 1. Matrix metalloproteinase 8 plays a significant role in the inflammatory process. Developmental Endothelial Locus 1 acts as a crucial immunomodulator, maintaining tissue homeostasis. Our findings reveal that 2-Hydroxyisocaproic acid inhibits the fragmentation of Developmental Endothelial Locus 1 by dose-dependently modulating and reducing the matrix metalloproteinase 8 activity. Notably, 2-Hydroxyisocaproic acid’s reversible inhibition of matrix metalloproteinase 8 does not eventually involve covalent bonding, positioning it as an enzyme modulator or down regulator rather than a direct inhibitor. This property of active matrix metalloproteinase 8 reduction by 2-Hydroxyisocaproic acid opens new avenues for therapeutic intervention, particularly in managing excessive inflammatory responses, such as the "cytokine storm" observed in lung tissue inflammation or arthritic joints like in osteoarthritis.