Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Signal Transduction: Overview01:26

Signal Transduction: Overview

Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Formation of Lipopolysaccharides01:19

Formation of Lipopolysaccharides

Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin, triggering...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Drugging endosomal flux.

Nature chemical biology·2026
Same author

Validating Natural Compounds as Toll-Like Receptor 4 (TLR4) Antagonists: Experimental Challenges and Therapeutic Perspectives.

Journal of medicinal chemistry·2025
Same author

Monosaccharide-Based Synthetic TLR4 Agonist Enhances Vaccine Efficacy against <i>Pseudomonas aeruginosa</i> Challenge.

ACS infectious diseases·2025
Same author

Towards more efficient synthetic immunomodulators: biological characterization and mechanism of action of monosaccharide-derived TLR4 agonists.

RSC medicinal chemistry·2025
Same author

Preclinical development of the TLR4 antagonist FP12 as a drug lead targeting the HMGB1/MD-2/TLR4 axis in lethal influenza infection.

Innate immunity·2025
Same author

Effects of the green cross-linking agent tannic acid and its oxidation on the properties of porcine plasma protein superabsorbent materials.

International journal of biological macromolecules·2025

Related Experiment Video

Updated: Jun 8, 2026

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
09:51

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling

Published on: July 26, 2017

Exploring the LPS/TLR4 signal pathway with small molecules.

Francesco Peri1, Matteo Piazza, Valentina Calabrese

  • 1Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy. francesco.peri@unimib.it

Biochemical Society Transactions
|September 25, 2010
PubMed
Summary

Researchers explored molecules that modulate Toll-like receptor 4 (TLR4) signaling, crucial for innate immunity. They identified small molecules targeting the LPS-CD14 interaction, showing potential for treating inflammatory conditions and pain.

More Related Videos

Using RNA-interference to Investigate the Innate Immune Response in Mouse Macrophages
12:47

Using RNA-interference to Investigate the Innate Immune Response in Mouse Macrophages

Published on: November 3, 2014

Real-time Imaging of Leukotriene B4 Mediated Cell Migration and BLT1 Interactions with &beta;-arrestin
13:45

Real-time Imaging of Leukotriene B4 Mediated Cell Migration and BLT1 Interactions with β-arrestin

Published on: December 23, 2010

Related Experiment Videos

Last Updated: Jun 8, 2026

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
09:51

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling

Published on: July 26, 2017

Using RNA-interference to Investigate the Innate Immune Response in Mouse Macrophages
12:47

Using RNA-interference to Investigate the Innate Immune Response in Mouse Macrophages

Published on: November 3, 2014

Real-time Imaging of Leukotriene B4 Mediated Cell Migration and BLT1 Interactions with &beta;-arrestin
13:45

Real-time Imaging of Leukotriene B4 Mediated Cell Migration and BLT1 Interactions with β-arrestin

Published on: December 23, 2010

Area of Science:

  • Immunology
  • Pharmacology

Background:

  • The discovery of Toll-like receptor 4 (TLR4) as a key bacterial endotoxin receptor has spurred interest in modulating innate immunity.
  • Lipopolysaccharide (LPS) sensing involves a cascade of receptors: LPS-binding protein (LBP), CD14, myeloid differentiation protein 2 (MD-2), and TLR4.

Purpose of the Study:

  • To review natural and synthetic molecules that modulate TLR4-mediated LPS signaling.
  • To discuss the mechanisms of action for these modulatory compounds.
  • To present novel small molecules targeting the LPS-CD14 interaction for therapeutic potential.

Main Methods:

  • Literature review of compounds affecting TLR4 pathway.
  • Classification of compounds based on molecular targets (LPS, LBP, CD14, MD-2, TLR4).
  • Description of proprietary small molecules inhibiting LPS-CD14 interaction.

Main Results:

  • Several molecules influencing TLR4-LPS signaling in humans and animals were identified.
  • Novel small molecules selectively inhibit LPS-stimulated TLR4 activation by targeting LPS-CD14.
  • These compounds demonstrated in vivo activity against septic shock, inflammation, and neuropathic pain.

Conclusions:

  • Modulating TLR4-mediated LPS signaling offers therapeutic opportunities.
  • Targeting the LPS-CD14 interaction with small molecules is a promising strategy.
  • The developed compounds show potential for treating inflammatory diseases and pain.