Abstract
Inflammatory responses are essential in eliminating harmful substrates from damaged tissue and inducing recovery. Several cytokines participate in and facilitate this response. Certain cytokines such as interleukin (IL)-1β and IL-18 are initially produced in precursor form in response to toll-like receptor (TLR) ligands and undergo maturation by inflammasomes, which are cytosolic multi-protein complexes containing nucleotide-binding oligomerization domain (NOD)-containing protein 2-like receptors (NLRs). Immune modulators targeting inflammasomes have been investigated to control inflammatory diseases such as metabolic syndrome. However, most immune modulators possessing anti-inflammasome properties attenuate production of other cytokines, which are essential for host defense. In this review, we analyzed the effect of anti-inflammasome agents on the production of cytokines which are not regulated by inflammasome and involving in initial immune responses. As a result, the inflammasome inhibitors are put into three categories: non-effector, stimulator, or inhibitor of cytokine production. Even the stimulator of cytokine production ameliorated symptoms resulting from inflammasome activation in mouse models. Thus, we suggest ideal immune modulators targeting inflammasomes in order to enhance cytokine production while inhibiting cytokine maturation.
Highlights
Inflammasomes, first introduced by Tschopp and his team in 2002, are multiprotein complexes formed by the mechanism in which inflammatory cytokines, interleukin (IL)-1β and IL-18, are converted from inactive precursors into active form and secreted[1]
Inflammasome activation can be divided into the priming and activation steps
The activation step induces the assembly of inflammasome components, resulting in cleavage of caspase-1 and the pro-forms of cytokines
Summary
Inflammasomes, first introduced by Tschopp and his team in 2002, are multiprotein complexes formed by the mechanism in which inflammatory cytokines, interleukin (IL)-1β and IL-18, are converted from inactive precursors into active form and secreted[1]. Extracts of garlic, onion, chive, and wild chive containing sulfur compounds were found to inhibit NLRP3 inflammasome activation[38] Overall, these sulfur compounds selectively attenuated inflammasome activation and cytokine expression at the priming step. MB inhibits both the activation of canonical inflammasomes such as NLRP3, NLRC4, and AIM2 as well as non-canonical inflammasomes It attenuates maturation of IL-1β and IL-18, secretion of active caspase-1, and formation of the ASC pyroptosome. The type of β-glucan extracted from shiitake mushroom LNT, which is known to have anti-cancer effects, enhances expression of inflammatory cytokines and inflammasome components as well as reduces activation of the AIM2 and non-canonical inflammasomes[50,51]. Similar to PGA, LNT is an ideal immune modulator targeting inflammasomes without loss of the inflammatory response against bacterial infection
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
