Differential expression of chemokines and chemokine receptors during microglial activation and inhibition

Sergey G. Kremlev, Rebecca L. Roberts, Charles Palmer

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Intrauterine infection produces an inflammatory response in the fetus characterized by increased inflammatory cytokines in the fetal brain and activation of brain microglial cells. Intrauterine infection can release bacterial cell wall products into the fetal circulation. Lipopolysaccharides (LPS) are derived from the cell walls of gram negative organisms. The degree of microglial cell activation may influence the extent of brain injury following an inflammatory stimulus. Chemokines, which are released by activated microglia, regulate the influx of inflammatory cells to the brain. Accordingly, therapeutic strategies that reduce the extent of chemokine expression in microglial cells may prove neuroprotective. Minocycline (MN), a semisynthetic tetracycline derivative, protects brain against global and focal ischemia in rodents and inhibits microglial cell activation. To determine if minocycline can reduce the production of chemokines and chemokine receptors in response to LPS, microglial-like BV-2 and HAPI cells were cultured in the presence or absence of 100 ng/ml of LPS. Enzyme-linked immunosorbent assay (ELISA) and semi-quantitative RT-PCR were used to examine changes in inflammatory chemokines (macrophage inflammatory protein-1 (MIP-1α), regulated upon activation, normal T cell expressed and secreted (RANTES), and inducible protein-10 (IP-10)) and chemokine receptor (C-C chemokine receptor 5 (CCR5) and C-X-C chemokine receptor 3 (CXCR3)) production, respectively. We found that in both cell lines chemokine release after 4-, 8-, and 16-h exposure to LPS was significantly higher compared to non-exposed cells for all the chemokines measured, P < 0.001. Minocycline inhibited chemokine release of LPS-stimulated BV-2 cells. There was even greater inhibition (up to 50%) of mRNA expression after exposure to LPS (P < 0.001). We conclude that endotoxin enhanced the expression of chemokines and chemokine receptors in microglial-like cell lines. Modulation of this expression was achieved with minocycline. Recognition of the mechanisms whereby minocycline exerts its anti-inflammatory effect on microglia may uncover specific targets for pharmacologic intervention.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalJournal of Neuroimmunology
Volume149
Issue number1-2
DOIs
StatePublished - Apr 1 2004

Fingerprint

Chemokine Receptors
Chemokines
Minocycline
Lipopolysaccharides
CC Chemokines
Brain
Microglia
Cell Wall
Macrophage Inflammatory Proteins
CXC Chemokines
Cell Line
Infection
Tetracycline
Endotoxins
Brain Injuries
Cultured Cells
Rodentia
Fetus
Anti-Inflammatory Agents
Ischemia

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

Cite this

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title = "Differential expression of chemokines and chemokine receptors during microglial activation and inhibition",
abstract = "Intrauterine infection produces an inflammatory response in the fetus characterized by increased inflammatory cytokines in the fetal brain and activation of brain microglial cells. Intrauterine infection can release bacterial cell wall products into the fetal circulation. Lipopolysaccharides (LPS) are derived from the cell walls of gram negative organisms. The degree of microglial cell activation may influence the extent of brain injury following an inflammatory stimulus. Chemokines, which are released by activated microglia, regulate the influx of inflammatory cells to the brain. Accordingly, therapeutic strategies that reduce the extent of chemokine expression in microglial cells may prove neuroprotective. Minocycline (MN), a semisynthetic tetracycline derivative, protects brain against global and focal ischemia in rodents and inhibits microglial cell activation. To determine if minocycline can reduce the production of chemokines and chemokine receptors in response to LPS, microglial-like BV-2 and HAPI cells were cultured in the presence or absence of 100 ng/ml of LPS. Enzyme-linked immunosorbent assay (ELISA) and semi-quantitative RT-PCR were used to examine changes in inflammatory chemokines (macrophage inflammatory protein-1 (MIP-1α), regulated upon activation, normal T cell expressed and secreted (RANTES), and inducible protein-10 (IP-10)) and chemokine receptor (C-C chemokine receptor 5 (CCR5) and C-X-C chemokine receptor 3 (CXCR3)) production, respectively. We found that in both cell lines chemokine release after 4-, 8-, and 16-h exposure to LPS was significantly higher compared to non-exposed cells for all the chemokines measured, P < 0.001. Minocycline inhibited chemokine release of LPS-stimulated BV-2 cells. There was even greater inhibition (up to 50{\%}) of mRNA expression after exposure to LPS (P < 0.001). We conclude that endotoxin enhanced the expression of chemokines and chemokine receptors in microglial-like cell lines. Modulation of this expression was achieved with minocycline. Recognition of the mechanisms whereby minocycline exerts its anti-inflammatory effect on microglia may uncover specific targets for pharmacologic intervention.",
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Differential expression of chemokines and chemokine receptors during microglial activation and inhibition. / Kremlev, Sergey G.; Roberts, Rebecca L.; Palmer, Charles.

In: Journal of Neuroimmunology, Vol. 149, No. 1-2, 01.04.2004, p. 1-9.

Research output: Contribution to journalArticle

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