Related Experiment Video

Updated: Jun 15, 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

IL-6 and high glucose synergistically upregulate MMP-1 expression by U937 mononuclear phagocytes via ERK1/2 and JNK

Yanchun Li1, Devadoss J Samuvel, Kamala P Sundararaj

  • 1Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, College of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.

Journal of Cellular Biochemistry
|March 13, 2010
PubMed

Insights

Interleukin-6 (IL-6) and high glucose significantly increase matrix metalloproteinase-1 (MMP-1) expression in immune cells. This synergistic effect involves the ERK, JNK pathways, and c-Jun upregulation, impacting inflammation-associated diseases.

Area of Science:

  • Biochemistry
  • Immunology
  • Molecular Biology

Background:

  • Matrix metalloproteinases (MMPs) are crucial in tissue remodeling and destruction during inflammation.
  • Interleukin-6 (IL-6) is a key pro-inflammatory cytokine, but its regulation of MMPs in mononuclear phagocytes is not fully understood.
  • The combined effects of IL-6 and hyperglycemia on MMP expression require further investigation.

Purpose of the Study:

  • To investigate the regulatory effect of IL-6, alone or with high glucose, on MMP-1 expression in U937 mononuclear phagocytes.
  • To elucidate the underlying molecular mechanisms, including signaling pathways and transcription factors involved in MMP-1 regulation.

Main Methods:

  • U937 mononuclear phagocytes were treated with IL-6 and/or high glucose.
  • MMP-1 expression and secretion were measured.
  • Extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and c-Jun expression/activity were analyzed.
  • RNA interference was used to suppress c-Jun expression.
  • Experiments were replicated in human primary monocytes.

Main Results:

  • IL-6 potently stimulated MMP-1 expression.
  • High glucose augmented IL-6-induced MMP-1 expression.
  • IL-6 and high glucose synergistically increased MMP-1 expression and secretion.
  • The ERK and JNK pathways were essential for IL-6 and high glucose-mediated MMP-1 stimulation.
  • IL-6 and high glucose upregulated c-Jun expression, which was critical for MMP-1 transcription.
  • These findings were consistent in both U937 cells and primary human monocytes.

Conclusions:

  • IL-6 and high glucose synergistically stimulate MMP-1 expression and secretion in mononuclear phagocytes.
  • The synergistic effect is mediated through the activation of ERK and JNK signaling pathways and subsequent upregulation of c-Jun.
  • These findings provide insights into the molecular mechanisms underlying inflammation-associated diseases, particularly in the context of hyperglycemia.

Related Concept Videos

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...
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...
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
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...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...