Mirza Saqib Baig
Indian Institute of Technology, India
Title: The TLR4-SOCS1-p38MAPK axis regulates macrophage polarization in response to Lipopolysaccharide
Biography
Biography: Mirza Saqib Baig
Abstract
Activated macrophages regulate the course, locality, duration and severity of inflammation. During the course of inflammation, distinct macrophage phenotypes have been observed. M1-macrophages are believed to be involved in the initiation and propagation of inflammation while M2 macrophages are apparently involved in the resolution of the inflammatory process. Therefore, identifying the regulatory mechanisms of macrophage phenotypic specification can be useful clinically to mitigate tissue damage and foment repair caused by dysregulated or persistent inflammatory conditions. Here we show that NOS1 regulation of suppressor of cytokine signaling-1 (SOCS1) stability in macrophages as a critical effector of macrophage phenotypic specification thereby indicating that NOS1 may be a clinically relevant drug target to suppress chronic inflammatory conditions. Further, increased amounts of SOCS1 in NOS1-/- macrophages leads to decreased p38MAPK activity, which impairs expression of M1 signature markers but not M1 genes. These data illustrate the molecular checkpoints involved in homeostatic macrophage polarization and suggest new therapeutic strategies to prevent inflammatory responses.