Simultaneous targeting of TIRAP and RIPK2: an effective approach for the treatment of chronic inflammatory diseases

Abstract

Chronic inflammation is a prolonged immune response characterized by the persistent activation of immune cells, leading to tissue damage and the development of various diseases, including cancer, cardiovascular disorders, and autoimmune conditions. Macrophages play a central role in chronic inflammation by producing pro-inflammatory cytokines and mediating the immune response to infections. In bacterial infection- associated chronic inflammation, key signaling pathways involving RIPK2 and TIRAP are activated. RIPK2 is a critical mediator downstream of receptors recognizing Gram-positive bacteria. Its activation triggers NF-κB and MAPK pathways, which results in the production of inflammatory cytokines. Similarly, TIRAP acts as an adaptor protein in the Toll-like receptor (TLR) signaling pathway, which detects bacterial components of Gram-negative bacteria. TIRAP facilitates the recruitment of downstream signaling molecules, amplifying the inflammatory response. Given their central roles in modulating immune responses, targeting both RIPK2 and TIRAP offers a promising therapeutic approach to mitigate chronic inflammation associated with bacterial infections. Inhibiting these pathways can effectively suppress the excessive production of pro-inflammatory cytokines, thereby reducing inflammation caused by both Gram-positive and Gram-negative bacteria. This dual-target strategy has the potential to provide a broad-spectrum therapeutic solution for treating bacterial infection-induced chronic inflammatory diseases.