Related Experiment Video

Updated: Jun 22, 2025

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
09:04

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

20.9K

Revealing the Mechanism of NLRP3 Inflammatory Pathway Activation through K+ Efflux Induced by PLO via Signal Point

Qiang Shan1,2, Wenbo Ma1, Bolin Li1

  • 1College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.

International Journal of Molecular Sciences
|June 27, 2024
PubMed

Insights

Trueperella pyogenes pyolysin (PLO) causes inflammatory damage. Specific mutations in PLO significantly reduced its inflammatory injury abilities, offering insights into cholesterol-dependent cytolysin mechanisms.

Area of Science:

  • Microbiology
  • Toxicology
  • Immunology

Background:

  • Trueperella pyogenes is an opportunistic pathogen.
  • Pyolysin (PLO) is a key virulence factor of T. pyogenes, belonging to the cholesterol-dependent cytolysin (CDC) family.
  • Understanding PLO's mechanism aids in comprehending the broader CDC protein family.

Purpose of the Study:

  • To investigate the inflammatory damage mechanism of Pyolysin (PLO).
  • To analyze the impact of specific point mutations on PLO's virulence.
  • To provide a theoretical basis for research on bacterial toxins.

Main Methods:

  • Establishment of a mouse muscle tissue model infected with recombinant PLO (rPLO).
  • Infection with single-point mutants: rPLO N139K and rPLO F240A.
  • Detailed examination of inflammatory mechanisms associated with PLO mutations.

Main Results:

  • Recombinant PLO (rPLO) induced inflammatory damage in the mouse model.
  • Mutants rPLO N139K and rPLO F240A showed significantly reduced inflammatory injury capabilities compared to wild-type rPLO.
  • Specific point mutations demonstrably alter the inflammatory potential of PLO.

Conclusions:

  • The study elucidates the inflammatory mechanism of PLO through analysis of its point mutations.
  • Findings highlight the critical role of specific amino acid residues in PLO-mediated inflammation.
  • This research offers significant theoretical and practical implications for future studies on bacterial toxins and pathogenesis.
Keywords:
K+ effluxNLRP3PLOTrueperella pyogenescholesterol-dependent cytolysinsingle-point mutation

More Related Videos

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages06:52

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages

Published on: May 21, 2018

10.7K
Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

3.2K

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.4K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.5K
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.4K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.3K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.4K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K