DPP4 regulates the inflammatory response in a rat model of febrile seizures

Issue title: Selected papers from the 6th China–France International Symposium “Stem Cells and Regenerative Medicine” and the first meeting of the France–China International CNRS Network (GDRI) CeSMeR, Nancy, 10–13 July 2016

Guest editors: J.-F. Stoltz, J. Magdalou and D. Bensoussan

Article type: Research Article

Authors: Sun, Qi^a | Zhang, Yusong^a | Huang, Jie^a | Yu, Fang^b | Xu, Jian^e | Peng, Biwen^c | Liu, Wanhong^d | Han, Song^a | Yin, Jun^{a; *} | He, Xiaohua^a

Affiliations: [a] Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China | [b] Department of Pathology, Zhongnan Hospital, Wuhan University, Wuhan, China | [c] Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan, China | [d] Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, China | [e] Weifang Maternity and Child Hospital, Weifang, China

Correspondence: [*] Corresponding author: Jun Yin, School of Basic Medical Sciences, Wuhan University, Donghu Road No. 185, Wuchang, Wuhan 430071, China. Tel.: 86-27-68759991; Fax: 86-27-68759991; E-mail: [email protected].

Abstract: Febrile seizures (FS) are the most common seizure disorders in children aged 6 months to 5 years. Children suffering from complex FS have a high risk of developing subsequent temporal lobe epilepsy (TLE). Neuroinflammation is involved in the pathogenesis of FS although the mechanism remains unknown. Our previous study using the Whole Rat Genome Oligo Microarray determined that Dipeptidyl peptidase IV (DPP4) is potentially a related gene in FS rats. In this study, we demonstrated that DPP4 expression was significantly increased at both the protein and mRNA levels after hyperthermia induction. Sitagliptin, a specific enzyme inhibitor of DPP4, remarkably attenuated the severity of seizures in FS rats, and hyperthermia-induced astrocytosis was suppressed after DPP4 inhibition. Furthermore, sitagliptin significantly decreased the levels of the inflammatory cytokines IL-1β, TNF-α, and IL-6 but not IL-10. In addition, sitagliptin prevented NF-κB activation by decreasing phosphorylation of the p65 subunit. Taken together, our findings demonstrate that DPP4 functions as a critical regulator of neuroinflammation in hyperthermia-induced seizures and the DPP4 inhibitor may be a viable option for FS therapeutics.

Keywords: Febrile seizures, DPP4, sitagliptin, neuroinflammation, NF-κB

DOI: 10.3233/BME-171635

Journal: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S139-S152, 2017