Superoxide dismutase 1 overexpression reduces MCP-1 and MIP-1 alpha expression after transient focal cerebral ischemia.
Proinflammatory cytokines and chemokines are quickly upregulated in response to ischemia/reperfusion (I/R) injury; however, the relationship between I/R-induced oxidative stress and cytokine/chemokine expression has not been elucidated. We investigated the temporal profile of cytokine and chemokine gene expression in transient focal cerebral ischemia using complementary DNA array technology. Among 96 genes studied, 10, 4, 11, and 5 genes were increased at 6, 12, 24, and 72 h of reperfusion, respectively, whereas, 4, 11, 8, and 21 genes, respectively, were decreased. To clarify the relationship between chemokines and oxidative stress, we compared the gene and protein expression of monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) in wild-type (WT) mice and copper/zinc-superoxide dismutase (SOD 1) transgenic (Tg) mice. Monocyte chemoattractant protein-1 and MIP-1 alpha mRNA were significantly upregulated at 6 to 12 h of reperfusion. In the SOD 1 Tg mice, however, MCP-1 and MIP-1 alpha mRNA expression was significantly decreased 12 h postinsult. In the WT mice, MCP-1 and MIP-1 alpha protein expression peaked 24 h after onset of reperfusion determined by immunohistochemistry. In the SOD 1 Tg mice, MCP-1 and MIP-1 alpha immunopositive cells were reduced, as were concentrations of these proteins (measured by enzyme-linked immunosorbent assay) at 24 h of reperfusion. Our results suggest that MCP-1 and MIP-1 alpha expression is influenced by I/R-induced oxidative stress after transient focal stroke.
Nishi
Tatsuro
T
Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA.
Maier
Carolina M
CM
Hayashi
Takeshi
T
Saito
Atsushi
A
Chan
Pak H
PH
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics*; D054407:Chemokine CCL4; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D002546:Ischemic Attack, Transient / Q000235:genetics*; D007700:Kinetics; D019402:Macrophage Inflammatory Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D015427:Reperfusion Injury; D013482:Superoxide Dismutase / Q000235:genetics / Q000494:pharmacology*; D000072105:Superoxide Dismutase-1
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018925:Chemokines; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1