Monocyte chemoattractant protein-1-deficiency impairs the expression of IL-6, IL-1β and G-CSF after transient focal ischemia in mice.

Abstract

Monocyte chemoattractant protein-1 (MCP-1), a chemokine secreted by neurons and astrocytes following stroke is known to aggravate ischemia-related damage. Previous studies revealed that MCP-1-deficient mice develop smaller infarcts and have an improved neurological outcome, whereas mice overexpressing MCP-1 show worsened brain damage and impaired neurological function. The aim of the present study was to elucidate the molecular background of the enhanced recovery in MCP-1-deficient mice after stroke. For this purpose, we (1) performed expression analyses on crucial post-stroke related inflammatory genes in MCP-1-deficient mice compared to wildtype controls, (2) analyzed a possible impact of MCP-1 on astrocyte activation (3) investigated the cellular origin of respective inflammatory cytokines and (4) analyzed the impact of MCP-1 secretion on the migration of both neutrophil granulocytes and T-cells. Here we report that MCP-1-deficiency leads to a shift towards a less inflammatory state following experimental occlusion of the middle cerebral artery including an impaired induction of interleukin-6, interleukin-1β and granulocyte-colony stimulating factor expression as well as a subsequent diminished influx of hematogenous cells. Additionally, MCP-1-deficient mice developed smaller infarcts 36 hours after experimental stroke. Investigations revealed no differences in transcription of tumor necrosis factor-α and astrogliosis 12 and 36 hours after onset of ischemia. These novel results help to understand post ischemic, inflammatory mechanisms and might give further arguments towards therapeutical interventions by modulation of MCP-1 expression in post stroke inflammation.

• Authors: Jan-Kolja Strecker, Jens Minnerup, Burkhard Gess, E Bernd Ringelstein, Wolf-Rüdiger Schäbitz, Matthias Schilling
• Journal: PloS one (PLoS One) Vol. 6 Issue 10 Pg. e25863 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 22031820 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CCL2
• Interleukin-1beta
• Interleukin-6
• Tumor Necrosis Factor-alpha
• Granulocyte Colony-Stimulating Factor

Topics

• Animals
• Brain Ischemia (genetics, metabolism)
• Chemokine CCL2 (deficiency, genetics, metabolism)
• Granulocyte Colony-Stimulating Factor (genetics, metabolism)
• Immunohistochemistry
• Interleukin-1beta (genetics, metabolism)
• Interleukin-6 (genetics, metabolism)
• Laser Capture Microdissection
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Mutant Strains
• Real-Time Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (genetics, metabolism)