The Serine Protease-Serine Protease Inhibitor Regulatory Network in Inflammatory Bowel Disease: From Molecular Mechanisms to Novel Therapeutic Horizons

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that presents a significant global health challenge. Although its exact etiology remains unclear, growing evidence indicates that dysregulation of the complex regulatory network of serine proteases and their inhibitors is a major contributor to IBD pathogenesis. This imbalance leads to both pro-inflammatory and protective effects within the inflamed intestine, highlighting the need to better understand the underlying mechanisms. AIMS OF REVIEW: This review synthesizes recent advances in our understanding of the roles that host-derived serine proteases and their inhibitors play in intestinal inflammation. We assess current therapeutic approaches targeting this network, and explore the potential for developing novel serine protease inhibitors and more effective drug delivery systems. KEY SCIENTIFIC CONCEPTS OF REVIEW: The review discusses the pathophysiological roles of serine proteases and serpins, highlighting their dual functions in both promoting and regulating intestinal inflammation. It then evaluates existing and emerging therapeutic strategies that modulate this enzymatic network for the treatment of IBD. Finally, the review discusses future directions, emphasizing the development of next-generation inhibitors and the critical need for translational research to accelerate the clinical application of these promising therapies.