title: Caspase-1-independent Maturation of IL-1β in Ischemic Brain Injury: is there a Role for Gelatinases?
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.
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, via P. Bucci, ed. Polifunzionale, 87036, Rende (CS), Italy. amantea@unical.it.
authors.forename: Diana
authors.initials: D
authors.lastname: Amantea
authors.forename: Rossella
authors.initials: R
authors.lastname: Russo
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Certo
authors.forename: Laura
authors.initials: L
authors.lastname: Rombolà
authors.forename: Annagrazia
authors.initials: A
authors.lastname: Adornetto
authors.forename: Luigi A
authors.initials: LA
authors.lastname: Morrone
authors.forename: Maria Tiziana
authors.initials: MT
authors.lastname: Corasaniti
authors.forename: Giacinto
authors.initials: G
authors.lastname: Bagetta
mesh_terms: D001930:Brain Injuries / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D020170:Caspase 1; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D020170:Caspase 1; D018093:Gelatinases