Related Experiment Video

Updated: Jan 4, 2026

Rapid and Refined CD11b Magnetic Isolation of Primary Microglia with Enhanced Purity and Versatility
07:54

Rapid and Refined CD11b Magnetic Isolation of Primary Microglia with Enhanced Purity and Versatility

Published on: April 13, 2017

10.3K

Upregulation of IFN-β induced by Sema4D-dependent partial Erk1/2 inhibition promotes NO production in microglia

Ryo Tsuchihashi1, Toshinori Sawano2, Fumiya Watanabe1

  • 1Group of Neurobiology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Japan.

Biochemical and Biophysical Research Communications
|November 12, 2019
PubMed

Insights

Semaphorin 4D (Sema4D) enhances nitric oxide (NO) production in microglia by partially inhibiting Erk1/2 phosphorylation and upregulating Interferon-beta (IFN-β). This mechanism is crucial for microglial immune responses following cerebral ischemia.

Area of Science:

  • Neuroimmunology
  • Molecular Neuroscience

Background:

  • Semaphorin 4D (Sema4D) and its receptors, PlexinB1 and CD72, regulate critical cellular functions.
  • Previous research indicated Sema4D's role in increasing nitric oxide (NO) production in microglia post-cerebral ischemia.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which Sema4D enhances microglial NO production.
  • To investigate the involvement of Erk1/2 phosphorylation and Interferon-beta (IFN-β) in Sema4D-mediated NO upregulation.

Main Methods:

  • Primary microglia and cortical microglia were utilized.
  • Assessed the effects of Sema4D on NO production and Erk1/2 phosphorylation.
  • Investigated the role of Erk1/2 inhibition on NO production and IFN-β expression.
  • Analyzed IFN-β mRNA expression in the ischemic cortex of Sema4D-deficient mice.

Main Results:

  • Sema4D promoted NO production and slightly inhibited Erk1/2 phosphorylation in microglia.
  • Partial inhibition of Erk1/2 phosphorylation led to enhanced microglial NO production.
  • Erk1/2 inhibition induced Interferon-beta (IFN-β) mRNA expression, which in turn promoted NO production.
  • Sema4D deficiency downregulated IFN-β mRNA expression in the ischemic cortex.

Conclusions:

  • Sema4D enhances microglial NO production through a pathway involving partial Erk1/2 inhibition.
  • Upregulation of IFN-β is a key mediator in Sema4D-induced NO production.
  • These findings provide insight into the neuroimmune mechanisms following cerebral ischemia.
Keywords:
Erk1/2IFN-βMicrogliaNOSema4D

More Related Videos

Development of an Insert Co-culture System of Two Cellular Types in the Absence of Cell-Cell Contact11:29

Development of an Insert Co-culture System of Two Cellular Types in the Absence of Cell-Cell Contact

Published on: July 17, 2016

28.6K
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates09:12

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates

Published on: January 30, 2014

16.6K

Related Concept Videos

Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.7K
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...
9.7K
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...
2.9K
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...
2.0K