Differential production of MCP-1 and cytokine-induced neutrophil chemoattractant in the ischemic brain after transient focal ischemia in rats

Abstract

Chemokines have been shown to play an important role in leukocyte infiltration into ischemic lesions. Recently, the increased expression of monocyte chemoattractant protein-1 (MCP-1) and cytokine-induced neutrophil chemoattractant (CINC) was observed in experimental stroke models where infiltrated leukocytes were supposed to induce tissue injury, however, the protein level and time course of these chemokines have not been fully elucidated. Therefore, we analyzed the timedependent production of MCP-1 and CINC in the rat brain after transient middle cerebral artery occlusion (MCAO) by means of specific enzymelinked immunosorbent assay systems. The MCP-1 levels in the ipsilateral hemispheres increased from 6 h, peaked at 2 days, and thereafter gradually decreased. The peak MCP-1 concentration was 89.2 ؎ 28.2 ng/g tissue wet weight (mean ؎ SEM, n ‫؍‬ 5, 49.3-fold greater than the contralateral value at the same time, P F 0.05), which is supposed to be high enough to exert its biological effects. In contrast, the maximum CINC concentration that corresponded to 2.9 ؎ 0.7 ng/g tissue wet weight (mean ؎ SEM, n ‫؍‬ 5, 55.0-fold greater than the contralateral value at the same time, P F 0.05), was observed at 6 h. In addition, we confirmed the temporal profile of leukocyte subtypes that infiltrated into the ischemic brain, thus, neutrophil infiltration occurred at early stages (1-3 days), followed by massive infiltration of macrophages at later stages (2-7 days). These studies suggest that MCP-1 in cerebral ischemia actually plays a significant role in the migration of macrophages into the lesion and that the differential temporal production of these chemokines contributes to the regulation of infiltrated leukocyte subtypes. J. Leukoc. Biol. 65: 744-749; 1999.

Brain Cytokines and Chemokines: Roles in Ischemic Injury and Pain

“…Enhanced expression of mRNAs for monocyte chemoattractant protein-1 (MCP-1, CCL2) (26 -28), and macrophage inflammatory protein-1α (MIP-1α, CCL3) (26,29) was demonstrated in the ischemic brain using a rat MCAO model. Increase in the peptide contents of MCP-1 / CCL2 has been also shown in the brain after the ischemic insult (30). Cell species expressing these chemokine mRNAs were examined by a double in situ hybridization technique (28,29).…”

Soluble TNF Receptor 1-Secreting ex Vivo-Derived Dendritic Cells Reduce Injury After Stroke

“…After ischemia, messenger RNA expression of potent inflammatory cytokines and chemokines TNF-a, IL-1b, and MCP-1 increases in the brain within 1 to 3 hours and peaks between 24 and 36 hours. [4][5][6][7][8][9][10] Increases in protein levels of these factors occur by 6 hours after stroke (ref. 4 and our data) in neurons, glia, peripheral immune organs, and circulating immune cells.…”

Neuronal Injury Induces Cytokine-Induced Neutrophil Chemoattractant-1 (CINC-1) Production in Astrocytes

“…It has been reported that the levels of proinflammatory cytokines such as tumor necrosis factor-α and interleukin-1β, chemokines such as monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1α are markedly increased in the brain after middle cerebral artery occlusion (3 -6). Cytokine-induced neutrophil chemoattractant-1 (CINC-1), a member of the CXC chemokine family, is also upregulated in the ischemic brain (5,7,8). Under ischemic conditions, leukocytes infiltrate into the brain parenchyma from the circulation.…”