Alpha-melanocyte stimulating hormone suppresses intracerebral tumor necrosis factor-alpha and interleukin-1beta gene expression following transient cerebral ischemia in mice.
Following stroke, an intracerebral inflammatory response develops that may contribute to postischemic central nervous system injury. This study's objective was to determine whether the anti-inflammatory neuropeptide alpha-melanocyte stimulating hormone (MSH) can suppress postischemic activation of intracerebral tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) gene expression. Ipsilateral TNF-alpha levels were increased in cerebrocortical territory of the middle cerebral artery (MCA) following transient unilateral MCA occlusion (MCAO) and reperfusion in mice, and systemic alpha-MSH treatment (0.5 mg/kg i.p.) suppressed this increase. Systemic alpha-MSH treatment also inhibited the marked increases in cortical TNF-alpha and IL-1beta mRNA levels following MCAO, and reduced the intracerebral TNF-alpha protein levels seen after transient global ischemia. We conclude that alpha-MSH treatment suppresses intracerebral proinflammatory cytokine gene expression following transient cerebral ischemia, suggesting that systemically administered melanocortins may exert neuroprotective effects in cerebral ischemia.
Huang
Qinheng
Q
Division of Endocrinology, Diabetes, Metabolism and Molecular Medicine, Department of Medicine and the Tupper Research Institute, Tufts-New England Medical Center, 750 Washington Street, Boston, MA 02111, USA.
Tatro
Jeffrey B
JB
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D007839:Functional Laterality; D015870:Gene Expression / Q000187:drug effects*; D020244:Infarction, Middle Cerebral Artery; D007375:Interleukin-1 / Q000096:biosynthesis*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D015424:Reperfusion / Q000009:adverse effects; D013687:Telencephalon / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D000521:alpha-MSH / Q000494:pharmacology*
D018712:Analgesics, Non-Narcotic; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000521:alpha-MSH