Related Experiment Video
Updated: Jul 19, 2026
11:29
Development of an Insert Co-culture System of Two Cellular Types in the Absence of Cell-Cell Contact
Published on: July 17, 2016
S100B binding to RAGE in microglia stimulates COX-2 expression.
Roberta Bianchi1, Cecilia Adami, Ileana Giambanco
1department of Experimental Medicine and Biochemical Sciences, Sect. Anatomy, University of Perugia, Via del Giochetto C.P. 81 Succ. 3, 06122 Perugia, Italy.
Journal of Leukocyte Biology
|October 7, 2006
Summary
The protein S100B, released from astrocytes, influences brain cells. It promotes neuron growth at low doses but causes cell death at high doses, impacting neuroinflammation.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- S100B protein regulates intracellular functions in astrocytes.
- Extracellular S100B affects astrocytes, neurons, and microglia, with concentration-dependent effects.
- Neuronal responses to S100B are mediated by the receptor for advanced glycation end products (RAGE).
Purpose of the Study:
- To investigate the mechanism by which S100B up-regulates cyclooxygenase-2 (COX-2) in microglia.
- To determine the role of RAGE in S100B-induced microglial activation.
- To elucidate the signaling pathways involved in S100B-mediated COX-2 expression.
Main Methods:
- Primary microglia cultures were used to study S100B effects.
- Western blotting and ELISA were employed to measure protein expression and NO release.
- Specific inhibitors and small interfering RNAs (siRNAs) were used to block signaling pathways (Cdc42, Rac1, JNK, Ras, NF-kappaB).
Main Results:
- S100B up-regulates cyclooxygenase-2 (COX-2) expression in microglia.
- This up-regulation is RAGE-dependent and occurs independently of cofactors.
- S100B activates two distinct signaling pathways: Cdc42-Rac1-JNK and Ras-Rac1-NF-kappaB.
Conclusions:
- S100B acts as an astrocytic endokine, released into the extracellular space during brain insults.
- S100B contributes to neuroinflammation by activating microglia and up-regulating COX-2.
- Targeting S100B or its downstream pathways may offer therapeutic strategies for brain injuries.
Related Concept Videos
02:26NF-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 heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
01:09GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...