Danger- and pathogen-associated molecular patterns recognition by pattern-recognition receptors and ion channels of the transient receptor potential family triggers the inflammasome activation in immune cells and sensory neurons.

An increasing number of studies show that the activation of the innate immune system and inflammatory mechanisms play an important role in the pathogenesis of numerous diseases. The innate immune system is present in almost all multicellular organisms and its activation occurs in response to pathogens or tissue injury via pattern-recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Intracellular pathways, linking immune and inflammatory response to ion channel expression and function, have been recently identified. Among ion channels, the transient receptor potential (TRP) channels are a major family of non-selective cation-permeable channels that function as polymodal cellular sensors involved in many physiological and pathological processes.In this review, we summarize current knowledge of interactions between immune cells and PRRs and ion channels of TRP families with PAMPs and DAMPs to provide new insights into the pathogenesis of inflammatory diseases. TRP channels have been found to interfere with innate immunity via both nuclear factor-kB and procaspase-1 activation to generate the mature caspase-1 that cleaves pro-interleukin-1ß cytokine into the mature interleukin-1ß.Sensory neurons are also adapted to recognize dangers by virtue of their sensitivity to intense mechanical, thermal and irritant chemical stimuli. As immune cells, they possess many of the same molecular recognition pathways for danger. Thus, they express PRRs including Toll-like receptors 3, 4, 7, and 9, and stimulation by Toll-like receptor ligands leads to induction of inward currents and sensitization in TRPs. In addition, the expression of inflammasomes in neurons and the involvement of TRPs in central nervous system diseases strongly support a role of TRPs in inflammasome-mediated neurodegenerative pathologies. This field is still at its beginning and further studies may be required.Overall, these studies highlight the therapeutic potential of targeting the inflammasomes in proinflammatory, autoinflammatory and metabolic disorders associated with undesirable activation of the inflammasome by using specific TRP antagonists, anti-human TRP monoclonal antibody or different molecules able to abrogate the TRP channel-mediated inflammatory signals

Inflammasome Proteins as Biomarkers of Injury and Disease

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 apoptosis-associated 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 inflammasome-dependent 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