Caspase‐11 non‐canonical inflammasome: a critical sensor of intracellular lipopolysaccharide in macrophage‐mediated inflammatory responses

Yi, Young-Su

doi:10.1111/imm.12787

Cited by 189 publications

(221 citation statements)

References 89 publications

(264 reference statements)

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“…For example, Nakamura et al demonstrated that the NOD2 ligand muramyl dipeptide is transported from endosomes into the cytosol through endosomal membrane peptide transporters, solute carrier (SLC)15A3, and SLC15A4 in dendritic cells and macrophages. In addition, recent studies reported that LPS is released from Gram‐negative bacterium‐containing vacuoles into the cytosol by guanylate‐binding protein‐mediated lysis of the vacuoles and then directly binds to pro‐caspase‐11, leading to non‐canonical inflammasome activation in macrophages . The cytosolic entry mechanisms of microbial components, such as muramyl dipeptide and LPS, might be involved in those of lipoproteins and lipopeptides.…”

Section: Discussionmentioning

confidence: 99%

Activation of NLRP3 inflammasome in macrophages by mycoplasmal lipoproteins and lipopeptides

Saeki

Sugiyama

Hasebe

et al. 2018

Molecular Oral Microbiology

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The NLRP3 inflammasome, an intracellular sensor consisting of the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3), the adaptor protein apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), and procaspase-1, plays critical roles in host defense against microbial pathogens by inducing production of interleukin-1β (IL-1β) and IL-18. Mycoplasma salivarium and Mycoplasma pneumoniae cells activated murine bone marrow-derived macrophages (BMMs) to induce production of IL-1α, IL-1β, and IL-18. The IL-1β production-inducing activities of these mycoplasmas toward BMMs from Toll-like receptor 2 (TLR2)-deficient mice were significantly attenuated compared with those from C57BL/6 mice (B6BMMs). This result suggests the possibility that their lipoproteins as TLR2 agonists are involved in the activity. Lipoproteins of M. salivarium and M. pneumoniae (MsLP and MpLP), and the M. salivarium-derived lipopeptide FSL-1 induced IL-1β production by B6BMMs, but not by BMMs from caspase-1-, NLRP3- or ASC-deficient mice. The activities of MsLP and MpLP were not downregulated by the proteinase K treatment, suggesting that the active sites are their N-terminal lipopeptide moieties. B6BMMs internalized the mycoplasmal N-terminal lipopeptide FSL-1 at least 30 min after incubation, FSL-1-containing endosomes started to fuse with the lysosomes around 2 hours, and then FSL-1 translocated into the cytosol from LAMP-1 endosomes. The artificial delivery of FSL-1 into the cytosol of B6BMMs drastically enhanced the IL-1β production-inducing activity. FSL-1 as well as the representative NLRP3 inflammasome activator nigericin induced the NLRP3/ASC speck, but FSL-1 located in a compartment different from the NLRP3/ASC speck.

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Section: Discussionmentioning

confidence: 99%

Activation of NLRP3 inflammasome in macrophages by mycoplasmal lipoproteins and lipopeptides

Saeki

Sugiyama

Hasebe

et al. 2018

Molecular Oral Microbiology

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“…Intracellular PRRs induce inflammatory responses in a unique way by forming “inflammasomes,” intracellular protein complexes containing PRRs and inflammatory molecules . NLRs (e.g., NLRP1, NLRP3, and NLRC4) and AIM2 are activated by different stimuli and assemble “canonical inflammasomes” consisting of PRRs and pro‐caspase‐1 with or without the ASC.…”

Section: Inflammasomes: Structures and Activationmentioning

confidence: 99%

“…Caspase‐11 inflammasome is activated by directly interacting with intracellular LPS of Escherichia coli , Legionella pneumophilia , Salmonella typhimurium , Shigella flexneri , Citrobacter rodentium , and Burkholderia spp. Caspase‐11 inflammasome assembles by direct interaction between caspase‐11 CARD and LPS lipid A moiety (Figure E), allowing oligomerization of caspase‐11‐LPS (Figure F) . Caspase‐11 was initially discovered in mice, and recent studies identified caspase‐4 and ‐5 as human homologs of mouse caspase‐11 due to their ability to interact directly with intracellular LPS and to activate inflammasome pathways .…”

Section: Inflammasomes: Structures and Activationmentioning

confidence: 99%

“…Inflammation is a series of biological processes to protect the body from invading pathogens and danger signals/molecules of stressed cells . Inflammation is a host–defense mechanism mainly mediated by myeloid immune cells and characterized by redness, heat, pain, swelling, and loss of function .…”

Section: Introductionmentioning

confidence: 99%

“…Two categories of inflammasomes have been identified. The first category comprises “canonical inflammasomes,” including nucleotide‐binding oligomerization domain‐like receptors (NLRs) and absent in melanoma 2 (AIM2) inflammasomes, and the other category encompasses “non‐canonical inflammasomes,” including caspases‐4, ‐5, and ‐11 . Different ligands activate inflammasomes by assembling inflammasome components, thus inducing inflammatory responses …”

Section: Introductionmentioning

confidence: 99%

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Regulatory Roles of Flavonoids on Inflammasome Activation during Inflammatory Responses

2018

Molecular Nutrition Food Res

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Inflammation is an innate immune response to noxious stimuli to protect the body from pathogens. Inflammatory responses consist of two main steps: priming and triggering. In priming, inflammatory cells increase expressions of inflammatory molecules, while in triggering, inflammasomes are activated, resulting in cell death and pro-inflammatory cytokine secretion. Inflammasomes are protein complexes comprising intracellular pattern recognition receptors (PRRs) (e.g., nucleotide-binding oligomerization domain-like receptors (NLRs), absent in melanoma 2 (AIM2), and caspases-4/5/11) and pro-caspase-1 with or without a bipartite adaptor molecule ASC. Inflammasome activation induces pyroptosis, inflammatory cell death, and stimulates caspase-1-mediated secretion of interleukin (IL)-1b and IL-18. Flavonoids are secondary metabolites found in various plants and are considered as critical ingredients promoting health and ameliorating various disease symptoms. Anti-inflammatory activity of flavonoids and underlying mechanisms have been widely studied. This review introduces current knowledge on different types of inflammasomes and their activation during inflammatory responses and discusses recent studies regarding anti-inflammatory roles of flavonoids as suppressors of inflammasomes in inflammatory conditions. Understanding the regulatory effects of flavonoids on inflammasome activation will increase our knowledge of flavonoid-mediated anti-inflammatory activity and provide new insights into the development of flavonoid preparations to prevent and treat human inflammatory diseases.

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Inflammasome activation: from molecular mechanisms to autoinflammation

et al. 2022

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Inflammasomes are assembled by innate immune sensors that cells employ to detect a range of danger signals and respond with pro‐inflammatory signalling. Inflammasomes activate inflammatory caspases, which trigger a cascade of molecular events with the potential to compromise cellular integrity and release the IL‐1β and IL‐18 pro‐inflammatory cytokines. Several molecular mechanisms, working in concert, ensure that inflammasome activation is tightly regulated; these include NLRP3 post‐translational modifications, ubiquitination and phosphorylation, as well as single‐domain proteins that competitively bind to key inflammasome components, such as the CARD‐only proteins (COPs) and PYD‐only proteins (POPs). These diverse regulatory systems ensure that a suitable level of inflammation is initiated to counteract any cellular insult, while simultaneously preserving tissue architecture. When inflammasomes are aberrantly activated can drive excessive production of pro‐inflammatory cytokines and cell death, leading to tissue damage. In several autoinflammatory conditions, inflammasomes are aberrantly activated with subsequent development of clinical features that reflect the degree of underlying tissue and organ damage. Several of the resulting disease complications may be successfully controlled by anti‐inflammatory drugs and/or specific cytokine inhibitors, in addition to more recently developed small‐molecule inhibitors. In this review, we will explore the molecular processes underlying the activation of several inflammasomes and highlight their role during health and disease. We also describe the detrimental effects of these inflammasome complexes, in some pathological conditions, and review current therapeutic approaches as well as future prospective treatments.

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Caspase‐11 non‐canonical inflammasome: a critical sensor of intracellular lipopolysaccharide in macrophage‐mediated inflammatory responses

Cited by 189 publications

References 89 publications

Activation of NLRP3 inflammasome in macrophages by mycoplasmal lipoproteins and lipopeptides

Activation of NLRP3 inflammasome in macrophages by mycoplasmal lipoproteins and lipopeptides

Regulatory Roles of Flavonoids on Inflammasome Activation during Inflammatory Responses

Inflammasome activation: from molecular mechanisms to autoinflammation

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