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

Author(s): Diana Amantea, Rossella Russo, Michelangelo Certo, Laura Rombolà, Annagrazia Adornetto, Luigi A. Morrone, Maria Tiziana Corasaniti, Giacinto Bagetta.

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 16 , Issue 9 , 2016

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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.

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Article Details

VOLUME: 16
ISSUE: 9
Year: 2016
Page: [729 - 737]
Pages: 9
DOI: 10.2174/1389557516666160321112512
Price: $58

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