Related Experiment Video

Updated: Jun 13, 2026

Induction of Ocular Surface Inflammation and Collection of Involved Tissues
06:38

Induction of Ocular Surface Inflammation and Collection of Involved Tissues

Published on: August 4, 2022

IL-27 inhibits OSM-mediated TNF-alpha and iNOS gene expression in microglia

Brandi J Baker1, Keun W Park, Hongwei Qin

  • 1Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Glia
|May 15, 2010
PubMed

Insights

Oncostatin M (OSM) promotes inflammation and neurotoxicity in the central nervous system (CNS) via microglia. Interleukin-27 (IL-27) acts as a novel inhibitor, suppressing OSM

Area of Science:

  • Neuroimmunology
  • Cytokine Signaling

Background:

  • Elevated Oncostatin M (OSM) levels are linked to neurological conditions like multiple sclerosis (MS), HIV-associated neurocognitive disorder (HAND), and glioblastoma (GBM).
  • The precise role and mechanisms of OSM within the central nervous system (CNS) remain incompletely understood.

Purpose of the Study:

  • To investigate the effects of OSM on microglia, the primary immune cells of the CNS.
  • To elucidate the signaling pathways involved in OSM-induced microglial activation and its consequences.
  • To identify potential endogenous regulators of OSM-mediated inflammatory responses in the CNS.

Main Methods:

  • Investigated OSM-induced gene expression in microglia, focusing on pro-inflammatory mediators like tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS).
  • Analyzed the involvement of key signaling pathways, including NF-kappaB, JAK/STAT, and MAPK.
  • Assessed the neurotoxic potential of OSM-stimulated microglia and the modulatory effects of Interleukin-27 (IL-27).

Main Results:

  • OSM significantly induces TNF-alpha and iNOS production in microglia through an NF-kappaB-dependent pathway, partially involving TNF-R1 signaling.
  • OSM-induced microglial activation results in neurotoxicity.
  • IL-27 effectively suppresses OSM-mediated TNF-alpha and iNOS expression at the transcriptional level by inhibiting NF-kappaB activation and mitigates OSM-induced neurotoxicity.

Conclusions:

  • This study provides the first evidence of OSM's pro-inflammatory and neurotoxic effects mediated by microglia.
  • IL-27 emerges as a novel and potent inhibitor of OSM-induced inflammatory responses and neurotoxicity within the CNS.
  • These findings highlight a critical interplay between OSM and IL-27 in regulating neuroinflammation and offer potential therapeutic targets for CNS disorders.

More Related Videos

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

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...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
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 heterodimer of NF-κB...
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 (Humira),...
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
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 are of three kinds RI, RII, and RIII. The RI...