Brazilin-Ce nanoparticles attenuate inflammation by de/anti-phosphorylation of IKKβ

Shengxuan Li1, Kun Wang2, Kai Jiang1

  • 1State Key Laboratory of Cardiology, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.

Biomaterials
|January 7, 2024
PubMed

Insights

Novel Brazilin-Cerium nanoparticles (BX-Ce NPs) effectively reduce inflammation by inhibiting IKKβ phosphorylation. These nanoparticles show promise for treating inflammatory diseases like cardiovascular conditions and sepsis.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Inflammation Research

Background:

  • Protein phosphorylation/dephosphorylation is crucial in regulating inflammation.
  • Brazilin offers anti-inflammatory benefits but has a narrow therapeutic window.
  • Cerium (IV) nanoparticles can catalyze phosphoester bond hydrolysis.

Purpose of the Study:

  • To design and synthesize novel Brazilin-Cerium nanoparticles (BX-Ce NPs).
  • To investigate the anti-inflammatory effects of BX-Ce NPs by targeting IKKβ phosphorylation.
  • To evaluate the therapeutic potential of BX-Ce NPs in vivo models.

Main Methods:

  • Synthesis of Brazilin-Cerium nanoparticles (BX-Ce NPs).
  • In vitro assays to determine binding sites and inhibition of IKKβ phosphorylation.
  • In vivo studies using mouse models of myocardial infarction and sepsis.

Main Results:

  • BX-Ce NPs specifically bind to Asn225 and Lys428 of IKKβ, inhibiting its phosphorylation at Ser181 (IC50 = 2.5 μM).
  • BX-Ce NPs demonstrated significant anti-inflammatory effects in vitro.
  • In vivo studies showed amelioration of myocardial injury and improved survival in sepsis models.

Conclusions:

  • BX-Ce NPs exhibit potent anti-inflammatory activity by downregulating IKKβ phosphorylation.
  • These nanoparticles offer a promising therapeutic strategy for inflammation-related diseases.
  • BX-Ce NPs represent a novel approach for guided ion interference therapy targeting de/anti-phosphorylation.

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
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
140
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.9K
Inflammatory Bowel Disease IV: Pharmacological Management01:29

Inflammatory Bowel Disease IV: Pharmacological Management

Upon diagnosis, managing Inflammatory Bowel Disease (IBD) involves addressing several crucial aspects. The primary goals include resting the bowel, correcting malnutrition, and providing symptomatic relief. Resting the bowel may consist of medications to reduce inflammation and promote healing. Correcting malnutrition is essential, often requiring dietary adjustments and nutritional supplements. Symptomatic relief aims to ease pain, diarrhea, and other discomforts in IBD.
Pharmacologic...
128
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.5K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K