Related Experiment Video

Updated: Jun 14, 2026

Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes
11:48

Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes

Published on: May 31, 2018

Disaccharide derived from chondroitin sulfate A suppressed CpG-induced IL-6 secretion in macrophage-like J774.1 cells

Miao Jin1, Taku Iwamoto, Kiyoshi Yamada

  • 1Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. jinmiaollh@hotmail.com

Cytokine
|March 31, 2010
PubMed

Insights

A chondroitin sulfate derivative (Di-4S) effectively suppresses toll-like receptor 9 (TLR9)-induced interleukin-6 (IL-6) secretion from macrophages. This disaccharide inhibits key signaling proteins, offering potential for managing TLR9-mediated inflammation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • Toll-like receptor 9 (TLR9) ligands, like CpG, activate macrophages to secrete inflammatory cytokines such as interleukin-6 (IL-6).
  • This TLR9-mediated inflammatory response is crucial in innate immunity but can contribute to autoimmune diseases.

Purpose of the Study:

  • To investigate the effect of chondroitin sulfate derivatives on TLR9-induced IL-6 secretion in macrophages.
  • To elucidate the molecular mechanisms underlying the observed suppression of IL-6.

Main Methods:

  • Utilized macrophage-like J774.1 cell lines.
  • Stimulated cells with CpG to activate TLR9.
  • Administered chondroitin sulfate A (CS-A) and its derived disaccharide (Di-4S).
  • Measured IL-6 secretion at protein and mRNA levels.
  • Assessed the expression and degradation of signaling molecules, including IRAK1 and MyD88.

Main Results:

  • Chondroitin sulfate A (CS-A) did not suppress IL-6 secretion.
  • A specific disaccharide derived from CS-A (Di-4S) significantly suppressed both IL-6 protein and mRNA expression.
  • Di-4S inhibited the degradation of interleukin-1 receptor-associated kinase 1 (IRAK1) in the MyD88-dependent TLR9 signaling pathway.
  • Di-4S may also interfere with the direct interaction between CpG and TLR9.

Conclusions:

  • Oligosaccharides derived from chondroitin sulfates, particularly Di-4S, are potent suppressors of TLR9-mediated IL-6 secretion.
  • Di-4S acts by stabilizing IRAK1 and potentially disrupting CpG-TLR9 binding.
  • These findings suggest that chondroitin sulfate-derived oligosaccharides could be developed as therapeutic agents to control TLR9-driven inflammatory conditions.

More Related Videos

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
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...
Differentiation of Common Myeloid Progenitor Cells01:15

Differentiation of Common Myeloid Progenitor Cells

Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
Glycosaminoglycans01:23

Glycosaminoglycans

Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are long and linear polymers comprising of specific repeating disaccharides - the amino sugar that can be N-acetylglucosamine or N-acetylgalactosamine, and a uronic acid that is usually glucuronic acid or iduronic acid.
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...