Heterotrimeric complex of p38 MAPK, PKCδ, and TIRAP is required for AP1 mediated inflammatory response

摘要: Inflammation could be described as a physiological response of the body to tissue injury, pathogen invasion, and irritants. During inflammatory phase, cells both innate well adaptive immune system are activated recruited site inflammation. These mediators downstream targets for transcription factors; activator protein-1 (AP1), nuclear factor kappa-light-chain-enhancer (NF-κB), signal transducers activators factors (STAT1), interferon regulatory (IRFs), which control expression most immunomodulatory genes. There is significant increase in active p38 mitogen-activated protein kinase (p38MAK) immediately after lipopolysaccharide (LPS) stimulation, results activation AP-1 proinflammatory cytokines, IL-12 IL-23. We studied novel mechanism MAPK through formation heterotrimeric complex Protein C delta type (PKCδ), Toll-Interleukin 1 Receptor (TIR) Domain Containing Adaptor (TIRAP), proteins. TIRAP serves an adaptor molecule brings PKCδ close proximity. The facilitates p38MAPK by PKCδ. Therefore, we propose that disruption may good strategy dampen response. Structure-based design small molecules or peptides targetting PKCδ-TIRAP TIRAP-p38 interfaces would beneficial therapy AP1 mediated diseases.