PMID- 30593206 OWN - NLM STAT- MEDLINE DCOM- 20190114 LR - 20221005 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 97 IP - 52 DP - 2018 Dec TI - 1,25-dihydroxyvitamin-D3 promotes neutrophil apoptosis in periodontitis with type 2 diabetes mellitus patients via the p38/MAPK pathway. PG - e13903 LID - 10.1097/MD.0000000000013903 [doi] LID - e13903 AB - BACKGROUND: Abnormal neutrophils are involved in many chronic endocrine diseases, including type 2 diabetes mellitus (T2DM), and in periodontitis (PD), which is a chronic inflammatory disease in which neutrophils play a vital role. The p38 mitogen-activated protein kinase (MAPK) signaling pathway participates in the apoptosis of many inflammatory cells. Additionally, 1,25-dihydroxyvitamin-D3 (1,25VitD3) as a regulator can induce responses to infection and tumor cell apoptosis. However, the effect of 1,25VitD3 in the pathogenic relationship between T2DM and PD remains unclear. The aim of this study was to assess the effect of 1,25VitD3 on neutrophil apoptosis in patients with T2DM and PD and the p38-MAPK-relevant signaling pathway mechanism in this process in vitro. METHODS: Neutrophils were stained with Wright's stain, and apoptosis was detected by flow cytometry and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. Apoptosis- and p38-related mRNAs and proteins were examined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting and ELISA. The internal relationships were analyzed using a linear regression equation and Pearson's correlation coefficient. RESULTS: The highest rate of neutrophil apoptosis occurred in cultures treated with 10 mol/L 1,25VitD3 in the T2DM-PD group. The apoptosis rate in the T2DM-PD-p38 inhibitor group was higher than that in the healthy control group. Western blot, ELISA and qRT-PCR results showed that the mRNA and protein expression profiles of Caspase-3 and Bax were highly up-regulated and that Bcl-2 was down-regulated in the T2DM-PD-p38 inhibitor group. The expression levels of apoptotic mRNAs and proteins in the T2DM and T2DM-PD groups were significantly higher than those in the T2DM-p38 and T2DM-PD-p38 inhibitor groups. 1,25VitD3-induced neutrophil apoptosis and phosphorylated p38 (p-p38) expression were partially inhibited by the p38 inhibitor. Expression levels of apoptosis-related genes and p-p38 in neutrophils were positively associated with increasing concentrations of 1,25VitD3. p-p38 protein expression was positively associated with the level of serum 1,25VitD3. CONCLUSION: 1,25VitD3 could promote peripheral blood neutrophil apoptosis in patients with T2DM and PD through activation of the p38-MAPK signaling pathway in vitro. FAU - Tang, Yaping AU - Tang Y AD - Affiliated Hospital of Zunyi Medical University. AD - Department of Periodontology, Stomatological Hospital, Zunyi Medical University. FAU - Liu, Junyu AU - Liu J AD - Department of Oral and Maxillofacial Surgery, Xinqiao Hospital, Army Medical University. FAU - Yan, Yanmei AU - Yan Y AD - Department of Stomatology, First People's Hospital of Yueyang, China. FAU - Fang, Hui AU - Fang H AD - Affiliated Hospital of Zunyi Medical University. FAU - Guo, Chengwei AU - Guo C AD - Affiliated Hospital of Zunyi Medical University. FAU - Xie, Ruidi AU - Xie R AD - Affiliated Hospital of Zunyi Medical University. FAU - Liu, Qi AU - Liu Q AD - Affiliated Hospital of Zunyi Medical University. AD - Department of Periodontology, Stomatological Hospital, Zunyi Medical University. LA - eng PT - Journal Article PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (RNA, Messenger) RN - 0 (dihydroxy-vitamin D3) RN - 1406-16-2 (Vitamin D) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Apoptosis/drug effects/physiology MH - Culture Techniques MH - Diabetes Mellitus, Type 2/epidemiology/*physiopathology MH - Dose-Response Relationship, Drug MH - Female MH - Flow Cytometry MH - Humans MH - MAP Kinase Signaling System/*drug effects MH - Male MH - Neutrophils/*metabolism MH - Periodontitis/epidemiology/*physiopathology MH - RNA, Messenger MH - Real-Time Polymerase Chain Reaction MH - Vitamin D/*analogs & derivatives/pharmacology MH - p38 Mitogen-Activated Protein Kinases/drug effects PMC - PMC6314780 EDAT- 2018/12/30 06:00 MHDA- 2019/01/15 06:00 PMCR- 2018/12/28 CRDT- 2018/12/30 06:00 PHST- 2018/12/30 06:00 [entrez] PHST- 2018/12/30 06:00 [pubmed] PHST- 2019/01/15 06:00 [medline] PHST- 2018/12/28 00:00 [pmc-release] AID - 00005792-201812280-00082 [pii] AID - MD-D-18-04918 [pii] AID - 10.1097/MD.0000000000013903 [doi] PST - ppublish SO - Medicine (Baltimore). 2018 Dec;97(52):e13903. doi: 10.1097/MD.0000000000013903.