Crosstalk of toll-like receptors signaling and Nrf2 pathway for regulation of inflammation.

Abstract

Inflammation as a second line of defense of innate immunity plays a crucial role in eliminating invading pathogens (bacteria, viruses, fungi as well as other parasites). The inflammatory response may also activate adaptive immune system involving lymphocytes to mount either antibody dependent or cell-mediated immune responses to clear pathogenic insult. However, if continued, the inflammatory processes may become uncontrolled culminating in cellular injury and tissue destruction, thereby manifesting itself in chronic form. The chronic inflammation has been associated with numerous human pathological conditions like allergies and autoimmune diseases, atherosclerosis, arthritis, Alzheimer's disease, cancer, obesity, type 2 diabetes, schizophrenia, neuro-degenerative diseases and numerous others. The dysregulated inflammatory process is associated with overproduction of free radicals leading to oxidative stress and activation of different cell signaling pathways. The regulation of inflammation by TLR signaling as well as Nrf2 pathways separately is widely documented. Since both these major signaling pathways modulate inflammation, they may crosstalk to bring about coordinated inflammatory responses. The linkage between TLR signaling and Nrf2-Keap1 pathway may serve as a bridge between immune regulation and oxidative stress responses through regulation of inflammation. Also, inflammation is reportedly responsible for the plethora of diseased conditions; a study of its regulation by targeting the TLR-Nrf2 cross-talks may also be beneficial for the development of therapeutic therapies or prophylactic treatments. Hence, present review focuses on the crosstalk between TLR signaling and Nrf2 pathway with respect to their role in modulation of inflammation in normal as well as pathologic conditions.