Related Experiment Video

Updated: Jun 6, 2026

Adoptive Immunotherapy of iNKT Cells in Glucose-6-Phosphate Isomerase (G6PI)-Induced RA Mice
08:43

Adoptive Immunotherapy of iNKT Cells in Glucose-6-Phosphate Isomerase (G6PI)-Induced RA Mice

Published on: January 31, 2020

JNK1 controls mast cell degranulation and IL-1{beta} production in inflammatory arthritis

Monica Guma1, Jun-ichi Kashiwakura, Brian Crain

  • 1Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Pathology, Division of Rheumatology,School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.

Proceedings of the National Academy of Sciences of the United States of America
|December 8, 2010
PubMed

Insights

JNK1, not JNK2, drives joint destruction in rheumatoid arthritis by enabling mast cell degranulation and IL-1β release. JNK inhibition offers a promising therapeutic strategy for inflammatory arthritis.

Area of Science:

  • Immunology
  • Rheumatology
  • Molecular Biology

Background:

  • Rheumatoid arthritis (RA) is a chronic inflammatory condition characterized by significant bone and cartilage damage.
  • Existing biologic therapies provide benefits to a limited number of RA patients.
  • Targeting key pathogenic signaling pathways with small molecules presents an alternative therapeutic approach.

Purpose of the Study:

  • To investigate the role of c-Jun N-terminal kinase (JNK) isoforms, specifically JNK1 and JNK2, in the pathogenesis of inflammatory arthritis.
  • To determine if JNK1 is essential for joint swelling and destruction in a serum transfer arthritis model.
  • To explore the therapeutic potential of JNK inhibition in treating inflammatory arthritis.

Main Methods:

  • Utilized a serum transfer model of arthritis in mice to assess joint inflammation and destruction.
  • Investigated the specific roles of JNK1 and JNK2 in disease development.
  • Examined the impact of JNK1 deficiency on mast cell degranulation and cytokine production (IL-1β).
  • Assessed the efficacy of pharmacologic JNK inhibition in preventing and treating arthritis.

Main Results:

  • JNK1, but not JNK2, was found to be critical for joint swelling and destruction in the arthritis model.
  • The pro-inflammatory function of JNK1 was dependent on bone marrow-derived cells, particularly mast cells.
  • JNK1 deficiency impaired mast cell degranulation and reduced IL-1β release upon Fcγ receptor stimulation.
  • Pharmacologic inhibition of JNK effectively prevented arthritis onset and reduced joint swelling in established disease.

Conclusions:

  • JNK1 plays a crucial role in regulating mast cell degranulation and Fcγ receptor-mediated IL-1β production.
  • JNK1 also influences the biosynthesis of other pro-inflammatory cytokines and matrix metalloproteinases.
  • JNK1 represents an attractive therapeutic target for managing inflammatory arthritis.

Related Concept Videos

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...
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...
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...
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,...
NF-kB-dependent Signaling Pathway02:26

NF-kB-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...
Inflammation01:38

Inflammation

Overview