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Caspase-1-independent Maturation of IL-1β in Ischemic Brain Injury: is there a Role for Gelatinases?

[ Vol. 16 , Issue. 9 ]

Author(s):

Diana Amantea, Rossella Russo, Michelangelo Certo, Laura Rombolà, Annagrazia Adornetto, Luigi A. Morrone, Maria Tiziana Corasaniti and Giacinto Bagetta   Pages 729 - 737 ( 9 )

Abstract:


Ischemic stroke is a devastating condition primarily caused by reduced blood supply to the brain. Interleukin (IL)-1β is a pro-inflammatory cytokine that plays a pivotal role in the detrimental inflammatory processes that participate to cerebral ischemic damage. After injury, it is produced by distinct cells of the neurovascular unit as an inactive precursor, pro-IL-1β. Although previous studies have suggested that caspase-1 is the main enzyme implicated in the cleavage of pro-IL-1β into the biologically active cytokine, recent work has demonstrated that, under ischemia-reperfusion conditions, other mechanisms may be involved in cytokine maturation. Indeed, we have shown that in rats subjected to transient middle cerebral artery occlusion (MCAo), elevation of IL-1β levels is paralleled by an elevation of gelatinolytic, but not caspase-1 activity in the injured hemisphere and pharmacological inhibition of gelatinases, i.e. matrix metalloproteases (MMP)-2 and MMP-9 prevents cytokine maturation. These findings further support the hypothesis that, under ischemia-reperfusion injury, cerebral elevation of IL-1β occurs via mechanisms other than caspase-1, likely involving gelatinases.

Keywords:

Caspase-1, gelatinases, interleukin (IL)-1β, neuroinflammation, stroke.

Affiliation:

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, via P. Bucci, ed. Polifunzionale, 87036, Rende (CS), Italy



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