IL-18BP Alleviates Anxiety-Like Behavior Induced by Traumatic Stress via Inhibition of the IL-18R-NLRP3 Signaling Pathway in a Mouse Model of Hemorrhagic Shock and Resuscitation.

Autor: Zhang LM; Department of Anesthesiology, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine (Cangzhou No.2 Hospital), Cangzhou, China. azai2010@126.com.; Hebei Key Laboratory of Integrated Traditional and Western Medicine in Osteoarthrosis Research (Preparing), Cangzhou, China. azai2010@126.com., Zhang DX; Department of Gerontology, Cangzhou Central Hospital, Cangzhou, China., Song RX; Department of Anesthesiology, Cangzhou Central Hospital, Hebei Medical University, Cangzhou, China., Lv JM; Anesthesia and Trauma Research Unit, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine (Cangzhou No.2 Hospital), Cangzhou, China., Wang LY; Anesthesia and Trauma Research Unit, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine (Cangzhou No.2 Hospital), Cangzhou, China., Wu ZY; Department of Neurosurgery, Cangzhou Central Hospital, Hebei Medical University, Cangzhou, China., Miao HT; Department of Neurosurgery, Cangzhou Central Hospital, Hebei Medical University, Cangzhou, China., Zhou YB; Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Zhang W; Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Xin Y; Department of Anesthesiology, Cangzhou Central Hospital, Hebei Medical University, Cangzhou, China., Li Y; Department of Anesthesiology, Cangzhou Central Hospital, Hebei Medical University, Cangzhou, China.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2023 Jan; Vol. 60 (1), pp. 382-394. Date of Electronic Publication: 2022 Oct 21.
DOI: 10.1007/s12035-022-03085-x
Abstrakt: Psychological distress and posttraumatic stress, including anxiety, severely influence life quality. Previously, we reported that interleukin-18 (IL-18) was involved in pyroptosis-induced emotional changes in a rodent model of hemorrhagic shock and resuscitation (HSR). Here, we aimed to continue our investigation on the role of IL-18 binding protein (IL-18BP), which exhibits excellent anti-inflammatory effects as an IL-18 negative regulator. Mice were administered with an intraperitoneal injection of IL-18BP after HSR exposure and anxiety-like behavior was examined using the open-field test and elevated plus maze test. Moreover, the following variables post-HSR were measured: (1) the activation of astrocytes; (2) pyroptosis-associated factors including cleaved caspase-1, GSDMD, IL-18; (3) the roles of IL-18 receptor (IL-18R)-NOD-like receptor pyrin domain-containing-3 (NLRP3) signal with the application of the NLRP3 specific agonist or astrocyte-specific NLRP3 knockout mice. IL-18BP administration remarkably alleviated HSR-induced anxiety-like behavior, astrocytic activation, and increases in pyroptosis-associated factors, while NLRP3 agonist nigericin partially reversed IL-18BP-induced neuroprotective effects. Astrocyte-specific NLRP3 knockout mice exhibited relatively less anxiety-like behavior. Similarly, IL-18BP exhibited an anti-pyroptosis effect in astrocytes in an in vitro model of low oxygen-glucose deprivation. These findings offer unique perspectives on HSR-induced posttraumatic stress and indicate that inhibition of IL-18R-NLRP3 signal via IL-18BP can attenuate astrocytic activation and pyroptosis, broadening the therapeutic landscape for patients with psychological distress and posttraumatic stress.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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