title: Melatonin attenuates inflammation of acute pulpitis subjected to dental pulp injury.
abstract: Acute pulpitis (AP), one of the most common diseases in the endodontics, usually causes severe pain to the patients, which makes the search for therapeutic target of AP essential in clinic. Toll-like receptor 4 (TLR4) signaling is widely involved in the mechanism of pulp inflammation, while melatonin has been reported to have an inhibition for a various kinds of inflammation. We hereby studied whether melatonin can regulate the expression of TLR4/NF-ĸB signaling in the pulp tissue of AP and in human dental pulp cells (HDPCs). Two left dental pulps of the adult rat were drilled open to establish the AP model, and the serum levels of melatonin and pro-inflammatory cytokines, including interleukin 1β (IL-1β), interleukin 18 (IL-18) and tumor necrosis factor α (TNF-α), were assessed at 1, 3 and 5 d post injury. At the same time points, the expression of TLR4 signaling in the pulp was explored by quantitative real-time PCR and immunohistochemistry. The AP rats were administered an abdominal injection of melatonin to assess whether melatonin rescued AP and TLR4/NF-ĸB signaling. Dental pulp injury led to an approximately five-day period acute pulp inflammation and necrosis in the pulp and a significant up-regulation of IL-1β, IL-18 and TNF-α in the serum. ELISA results showed that the level of melatonin in the serum decreased due to AP, while an abdominal injection of melatonin suppressed the increase in serum cytokines and the percentage of necrosis at the 5 d of the injured pulp. Consistent with the inflammation in AP rats, TLR4, NF-ĸB, TNF-α and IL-1β in the pulp were increased post AP compared with the baseline expression. And melatonin showed an inhibition on TLR4/NF-ĸB signaling as well as IL-1β and TNF-α production in the pulp of AP rats. Furthermore, melatonin could also regulate the expression of TLR4/NF-ĸB signaling in LPS-stimulated HDPCs. These data suggested that dental pulp injury induced AP and reduced the serum level of melatonin and that supplementation with melatonin may have a protective effect on AP by modulating TLR4/NF-ĸB signaling in the pulp and in pulp cells.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, Fourth Military Medical University Xi'an, China ; Department of Stomatology, Jinan General Hospital of Jinan Military Region Jinan, China.
authors.forename: Ji-Guo
authors.initials: JG
authors.lastname: Li
authors.affiliation: Department of Neurology, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Jia-Ji
authors.initials: JJ
authors.lastname: Lin
authors.affiliation: Department of Stomatology, Jinan General Hospital of Jinan Military Region Jinan, China.
authors.forename: Zhao-Ling
authors.initials: ZL
authors.lastname: Wang
authors.affiliation: Department of Cardio-Thoracic Surgery, Kunming General Hospital of Chengdu Military Region Kunming, China.
authors.forename: Wen-Ke
authors.initials: WK
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, Fourth Military Medical University Xi'an, China.
authors.forename: Pei-Na
authors.initials: PN
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, Fourth Military Medical University Xi'an, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, Fourth Military Medical University Xi'an, China.
authors.forename: An-Sheng
authors.initials: AS
authors.lastname: Zhang
authors.affiliation: Department of Stomatology, Jinan General Hospital of Jinan Military Region Jinan, China.
authors.forename: Gao-Yi
authors.initials: GY
authors.lastname: Wu
authors.affiliation: Department of Stomatology, Jinan General Hospital of Jinan Military Region Jinan, China.
authors.forename: Guo-Xiong
authors.initials: GX
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, Fourth Military Medical University Xi'an, China.
authors.forename: Long-Xing
authors.initials: LX
authors.lastname: Ni
keywords: Acute pulpitis (AP); Toll-like receptor 4 (TLR4); dental pulp injury; melatonin; rat