Effects of cytokine deficiency on chemokine expression in CNS of mice with EAE

Agata Matejuk, Jami Dwyer, Atsushi Ito, Zachary Bruender, Arthur Vandenbark, Halina Offner

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Although both cytokines and chemokines have been implicated in the pathogenesis of clinical and histological EAE, their interactions in vivo have not yet been clearly established. To address this issue, we evaluated expression of chemokines and receptors in the CNS of wild-type control and cytokine deficient mice at the peak of EAE induced with MOG-35-55 peptide in CFA. Our results demonstrate that: 1) expression of most chemokines/receptors was drastically inhibited in TNF-α deficient mice, and was reflective of delayed onset and reduced severity of EAE; 2) distinct patterns of chemokine expression occurred in various other cytokine knockout mice that did not significantly affect expression of clinical EAE; 3) there was a strong association between expression of MIP-1α, MIP-2 and MCP-1 in CNS and overall severity of EAE in wild-type and cytokine knockout mice; and 4) among CNS infiltrating cells at the peak of EAE, macrophages and CD8+ T cells were the primary cellular source of most of the chemokines. Of note, we present evidence that TNF-α may be involved in regulating RANTES and MIP-1α, and that IL-4 may be involved in regulating MCP-1. Our results not only identify the cellular source of chemokines in CNS, but also implicate MIP-1α, MIP-2, and MCP-1 in controlling CNS inflammation and severity of EAE.

Original languageEnglish (US)
Pages (from-to)680-688
Number of pages9
JournalJournal of Neuroscience Research
Volume67
Issue number5
DOIs
StatePublished - Mar 1 2002

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Chemokines
Cytokines
Chemokine Receptors
Knockout Mice
Chemokine CCL5
Interleukin-4
Macrophages
Inflammation
T-Lymphocytes
Peptides

Keywords

  • Chemokines
  • Cytokines
  • EAE/MS
  • Rodent
  • Transgenic/knockout

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Effects of cytokine deficiency on chemokine expression in CNS of mice with EAE. / Matejuk, Agata; Dwyer, Jami; Ito, Atsushi; Bruender, Zachary; Vandenbark, Arthur; Offner, Halina.

In: Journal of Neuroscience Research, Vol. 67, No. 5, 01.03.2002, p. 680-688.

Research output: Contribution to journalArticle

Matejuk, Agata ; Dwyer, Jami ; Ito, Atsushi ; Bruender, Zachary ; Vandenbark, Arthur ; Offner, Halina. / Effects of cytokine deficiency on chemokine expression in CNS of mice with EAE. In: Journal of Neuroscience Research. 2002 ; Vol. 67, No. 5. pp. 680-688.
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