The role of IL-1β and neutrophil matrix metalloproteinase-9 in an animal model of Multiple Sclerosis

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B833
Abstract ID: 5326

Presenting Author:
Heather R Butler , Doctoral Student at Florida Atlantic Univ.

Abstract:

Multiple Sclerosis (MS) is a chronic inflammatory, autoimmune disease of the central nervous system (CNS) characterized by blood-brain barrier (BBB) disruption, CNS immune cell infiltration, demyelination, and neuronal loss. Key aspects of MS are recapitulated in the MS animal model experimental autoimmune encephalomyelitis (EAE). In EAE, neutrophils are known to contribute to BBB penetration. However, this mechanism is not well understood. Neutrophils are short-lived immune cells who are first responders in inflammatory reactions including proinflammatory signals such as interleukin-1β (IL-1β). In EAE and MS, IL-1β is linked to a potent autoimmune response and is known to induce matrix metalloproteinase-9 (MMP-9) resulting in a positive feedback loop. MMP-9 is an enzyme with diverse physiological roles and is linked to disease progression in EAE and MS. The interplay between MMP-9 and IL-1β in neutrophils in the context of EAE is unknown. 

Our preliminary studies showed increased gene expression and protein production of MMP-9 when IL-1β was administered into the CNS of mice. This elevated expression was abrogated with prior administration of a functional antibody against neutrophils, thus suggesting that infiltrating neutrophils could be responsible. The goal of this study is to further elucidate the interactivity of IL-1β and MMP-9 in EAE progression with a focus on the role of neutrophils.