title: DPP4 regulates the inflammatory response in a rat model of febrile seizures.
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.
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Yusong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pathology, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.affiliation: Weifang Maternity and Child Hospital, Weifang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Biwen
authors.initials: B
authors.lastname: Peng
authors.affiliation: Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Wanhong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000276:immunology*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006979:Hyperthermia, Induced / Q000009:adverse effects; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D003294:Seizures, Febrile / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D016328:NF-kappa B; D018819:Dipeptidyl Peptidase 4; D000068900:Sitagliptin Phosphate
keywords: DPP4; Febrile seizures; NF-κB; neuroinflammation; sitagliptin