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

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

Volume: 16 Issue: 9

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

Affiliation:

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

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.

Cite this article as:

Amantea Diana, Russo Rossella, Certo Michelangelo, Rombolà Laura, Adornetto Annagrazia, Morrone A. Luigi, Corasaniti Tiziana Maria and Bagetta Giacinto, Caspase-1-independent Maturation of IL-1β in Ischemic Brain Injury: is there a Role for Gelatinases?, Mini-Reviews in Medicinal Chemistry 2016; 16 (9) . https://dx.doi.org/10.2174/1389557516666160321112512