Monocyte chemottractant protein-1 activates a regional Th1 immunoresponse in nephritis of MRL/lpr mice

Sakiko Shimizu, Hitoshi Nakashima, Ken Nosuke Karube, Koichi Ohshima, Kensuke Egashira

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Objective. Monocyte chemoattractant protein-1 (MCP-1) is upregulated and recruits and activates inflammatory cells in nephritis of MRL lpr mice. It has been shown that anti-MCP-1 gene therapy is specifically effective in nephritis, while it was apparent that an imbalance towards Th1 predominance accelerates nephritis in MRL/lpr mice. The aim of this study was to clarify whether blockade of the MCP-1 signal by anti-MCP-1 gene therapy influences the Th1/Th2 balance in MRL/lpr mice. Method. An NH2-terminal deletion mutant of the MCP-1 gene (7ND) was injected into the skeletal muscles of MRL/lpr mice with advanced stage nephritis to suppress MCP-1 and its receptor (CCR2) signaling pathway. We evaluated the local tissue production of cytokines in splenocytes and microdissected infiltrating cells within the glomeruli or interstitium. Result. Although the production of cytokines in splenocytes was not influenced by anti-MCP-1 gene therapy, kidney glomeruli IL-12 mRNA production and interstitium-infiltrating cell production of IL-12 and IFN-γ mRNA were significantly reduced. Conclusion. The blockade of MCP-1 gene therapy does not influence helper T cell polarization, but acts directly on the regional Th1 immunoreaction in MRL/lpr mice.

Original languageEnglish
Pages (from-to)239-242
Number of pages4
JournalClinical and experimental rheumatology
Volume23
Issue number2
Publication statusPublished - Mar 1 2005

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Inbred MRL lpr Mouse
Nephritis
Chemokine CCL2
Monocytes
Genetic Therapy
Proteins
Interleukin-12
CCR2 Receptors
Kidney Glomerulus
Th1-Th2 Balance
Cytokines
Messenger RNA
Helper-Inducer T-Lymphocytes
Skeletal Muscle

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Monocyte chemottractant protein-1 activates a regional Th1 immunoresponse in nephritis of MRL/lpr mice. / Shimizu, Sakiko; Nakashima, Hitoshi; Karube, Ken Nosuke; Ohshima, Koichi; Egashira, Kensuke.

In: Clinical and experimental rheumatology, Vol. 23, No. 2, 01.03.2005, p. 239-242.

Research output: Contribution to journalArticle

Shimizu, Sakiko ; Nakashima, Hitoshi ; Karube, Ken Nosuke ; Ohshima, Koichi ; Egashira, Kensuke. / Monocyte chemottractant protein-1 activates a regional Th1 immunoresponse in nephritis of MRL/lpr mice. In: Clinical and experimental rheumatology. 2005 ; Vol. 23, No. 2. pp. 239-242.
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