Inflammasome proteins as biomarkers of injury and disease

Abstract

The inflammasome is a multi-protein complex of the innate immune response that activates caspase-1 after infections, tissue injury, or disease. Once active caspase-1 cleaves the pro-inflammatory cytokines pro-IL-1β and pro-IL-18 into their respective mature forms, IL-1β and IL-18. Inflammasome proteins such as caspase-1, NOD-like receptor protein-1 (NLRP1), NLRP3, or apoptosisassociated speck-like protein containing a CARD (ASC) can be used as biomarkers of tissue injury and disease. For instance, higher levels of inflammasome proteins are present in the cerebrospinal fluid of patients with traumatic brain injury who present poor outcomes after trauma. Hence, the inflammasome after brain injury can be used as a tool to prognosticate outcomes after brain trauma. Similarly, in rodent models of multiple sclerosis, animals that do not respond to the classic interferon (IFN)-β treatment do not present an NLRP3 inflammasomedependent disease. Thus, the inflammasome in multiple sclerosis can be used as a prognostic tool to identify responders to IFN-β treatment. In the same manner, patients taking finasteride for male pattern baldness who do not respond to treatment correlate with higher levels of caspase-1 in hair follicles. Moreover, the inflammasome can also be used as a biomarker of disease progression in diabetes and atherosclerosis, as well as a biomarker of tissue injury in inflammatory bowel disease and semen quality in patients with male infertility after spinal cord injury. Therefore, the inflammasome, a receptor of the innate immune response, is a useful biomarker in a variety of diseases and tissue injury.