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Updated: Apr 30, 2026

A Cryo-pulverization Protocol for Processing Mouse Paws to Evaluate Molecular Pathways of Tissue Inflammation in a Collagen Induced Arthritis Model
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A Cryo-pulverization Protocol for Processing Mouse Paws to Evaluate Molecular Pathways of Tissue Inflammation in a Collagen Induced Arthritis Model

Published on: October 30, 2019

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Alternative p38 MAPKs are essential for collagen-induced arthritis

Gabriel Criado1, Ana Risco, Dayanira Alsina-Beauchamp

  • 1Instituto de Investigación Sanitaria and Hospital Universitario 12 de Octubre, Madrid, Spain.

Arthritis & Rheumatology (Hoboken, N.J.)
|May 1, 2014
PubMed
Abstract

Insights

Mice lacking both p38γ and p38δ showed significantly reduced inflammatory arthritis severity. This indicates p38γ and p38δ are key regulators of joint destruction in collagen-induced arthritis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Rheumatology

Background:

  • The specific roles of p38 mitogen-activated protein kinase (MAPK) isoforms in inflammatory arthritis remain largely unknown.
  • This study focuses on p38γ and p38δ, two isoforms whose functions in arthritis have not been thoroughly investigated.

Purpose of the Study:

  • To investigate the role of p38γ and p38δ deficiency in the development and progression of collagen-induced arthritis (CIA).
  • To evaluate the impact of these deficiencies on immune responses and joint inflammation.

Main Methods:

  • Utilized wild-type, p38γ(-/-), p38δ(-/-), and combined p38γ/δ(-/-) knockout mice in a collagen-induced arthritis (CIA) model.
  • Assessed disease activity through semiquantitative scoring and histological analysis of joints.
  • Quantified serum cytokine levels, T cell cytokine responses, and anti-collagen antibody levels using flow cytometry, multiplex analysis, and ELISA.
  • Determined gene expression of cytokines and p38 MAPK isoforms in joints via quantitative PCR.

Main Results:

  • Combined deficiency of p38γ and p38δ markedly reduced arthritis severity and joint damage compared to wild-type mice.
  • Mice lacking both isoforms exhibited lower levels of pathogenic anti-collagen antibodies, interleukin-1β (IL-1β), and tumor necrosis factor α (TNFα).
  • In vitro T cell assays revealed reduced proliferation, interferon-γ (IFNγ), and IL-17 production in lymph node cells from p38γ/δ(-/-) mice.
  • Significantly inhibited IL-17 and IFNγ messenger RNA expression was observed in the joints of p38γ/δ(-/-) mice.

Conclusions:

  • The reduced disease severity in p38γ/δ(-/-) mice is linked to diminished cytokine production and antibody responses, highlighting p38γ and p38δ as critical regulators of inflammatory joint destruction in CIA.
  • These findings suggest that p38γ and p38δ are potential therapeutic targets for complex immune-mediated diseases like rheumatoid arthritis.

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