UT Southwest Biochemist and Breakthrough Award Dr. Zhijian "James" Chen's latest study answers the ancient issue of congenital immunity.
Scientists have long thought that one protein, NLRP3, can stimulate inflammation in response to many seemingly unrelated stimuli.
Dr. Chen, Professor of Molecular Biology and director of the UT Center for South East Inflammation Research, received the 2019 Life Sciences Award for identifying the DNA sensing enzyme cGAS (Cyclic GMP-AMP synthesis), which sounds like an alarm for an inherited immune response in cells.
The current study published today Nature, Dr. Chen studied another immune system pathway that included the NLRP3 protein, which is a significant component of the multiprotein complex called inflammacom. In response to too much of the harmful substances that range from toxins to cholesterol crystals, inflammation causes an inflammatory cell death or pyrotoze of the Greek word pyro, which means a fire. Inflammasome also increases the production of body immune systems, such as interleukins, which help in the body's immune response.
In addition, the NLRP3 protein is associated with an inflammation in the autoimmune disease group called cryoprine related periodic syndromes (CAPS), which includes the Family Cold Auto Inflammatory Syndrome (FCAS), gout, and Alzheimer's inflammatory form of the brain cells.
"The long-term issue in this area is how NLRP3 can activate many different agents that do not seem to belong to any chemical or structural similarity," said Dr Chen, a researcher at the Howard Hughes Medical Institute, who is the outstanding Department of Biomedical Sciences at George L. MacGregor, as Professor at the General Center for Genetic Studies at the Southwest University of Southwestern University. "These findings provide a new opportunity for the development of NLRP3 treatment for road infectious diseases."
Using a combination of biochemical, imagery and genetic approaches, Dr. Chen and a post-graduate researcher Dr. Jueqi Chen, a research leader with and without commitment, discovered changes in previously unknown structures in cells.
They found that various stimuli cause cell organelles, called the trans-Golgi network (TGN), to split into huge blister or fluid-filled sacos. These bubbles contain a specific lipid component (PI4P) that binds to a specific NLRP3 region. This binding triggers a series of events that stimulate inflammation activation.
"Inflammation of NLRP3 is unique, as it can be caused by a large amount of stimuli," said Dr. Chen "This study reveals that the NLRP3 inflammation reveals structural changes caused by a variety of different substances that cause cell damage, rather than directly recognizing the harmful factors. In fact, NLRP3 activation resembles the" security model "used by the plants to combat various threats by monitoring the host the goals that have changed, the so-called pathogen-induced, changed self-approach.
"In connection with the disassembled trans-Golgi network of bubbles as" altered oneself, "NLRP3 indirectly senses many pathogens and hazardous molecules," he added.