Chemokine receptor antagonist peptide, viral MIP-II, protects the brain against focal cerebral ischemia in mice.
The authors previously reported that mRNA for macrophage inflammatory protein-1alpha (MIP-1 alpha), a member of the CC chemokines, was expressed in glial cells after focal cerebral ischemia in rats. However, the function of chemokines in the ischemic brain remains unclear. Recently, viral macrophage inflammatory protein-II (vMIP-II), a chemokine analogue encoded by human herpesvirus-8 DNA, has been demonstrated to have antagonistic activity at several chemokine receptors. In the present study, the effects of vMIP-II and MIP-1alpha on ischemic brain injury were examined in mice to elucidate the roles of chemokines endogenously produced in the ischemic brain. Intracerebroventricular injection of vMIP-II (0.01-1 microg) reduced infarct volume in a dose-dependent manner when examined 48 hours after 1-hour middle cerebral artery occlusion followed by reperfusion. However, 1 microg MIP-1alpha increased infarct volume in the cortical region. These results supported the possibility that chemokines endogenously produced in the brain are involved in ischemic injury, and that chemokine receptors are potential targets for therapeutic intervention of stroke.
Takami
S
S
Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Minami
M
M
Nagata
I
I
Namura
S
S
Satoh
M
M
D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000494:pharmacology*; D019742:Chemokines, CC / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism; D007276:Injections, Intraventricular; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors*
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D019707:Receptors, Chemokine; C108059:vMIP-II