PMID- 37439265
OWN - NLM
STAT- MEDLINE
DCOM- 20230911
LR  - 20230911
IS  - 1600-0765 (Electronic)
IS  - 0022-3484 (Linking)
VI  - 58
IP  - 5
DP  - 2023 Oct
TI  - Human beta-defensins are correlated with the immune infiltration and regulated by 
      vitamin D(3) in periodontitis.
PG  - 986-996
LID - 10.1111/jre.13159 [doi]
AB  - OBJECTIVE: Exploring the correlation between human beta-defensins (HBDs) and immune 
      infiltration in periodontitis, and whether it is regulated by vitamin D(3) . 
      BACKGROUND: The human body produces essential antimicrobial peptides called HBDs, 
      which are associated with periodontitis. There is a strong link between 
      periodontal tissue destruction and the immune cell infiltration. Moreover, 
      vitamin D(3) has been reported to regulate the expression of immune cell 
      chemokines. However, the relationship between vitamin D(3) , HBDs, and immune 
      infiltration in periodontitis remains to be investigated. METHODS: The Gene 
      Expression Omnibus database was accessed to obtain transcriptomic information of 
      gingival samples taken from periodontitis patients. The expression value of HBD-2 
      and HBD-3 was calculated. Additionally, using the online program ImmuCellAl, 10 
      immune cells were scored for immune infiltration in the high-HBDs-expression 
      group and the low-HBDs-expression group, separately. After that, transcriptome 
      sequencing was done based on human gingival fibroblasts that had received vitamin 
      D(3) treatment. Furthermore, hGFs were treated by vitamin D(3) , tumor necrosis 
      factor-alpha (TNF-alpha), and Porphyromonas gingivalis lipopolysaccharide (Pg-LPS). The 
      expressions of HBD-2, HBD-3, interleukin-8 (IL-8), and monocyte chemoattractant 
      protein-1 (MCP-1) were detected. To seek the potential mechanism, CYP27A1 siRNA 
      was employed to reduce the expression of CYP27A1, and nuclear factor-gene binding 
      protein 65 (NF-kappaB p65) was examined. RESULTS: In GSE10334, the expressions of 
      HBD-2 and HBD-3 were down-regulated in periodontitis group. Meanwhile, monocyte, 
      macrophage, and CD4_T cell were less infiltrated in low-HBD-2-expression group, 
      while less Gamma-delta T-cell infiltration was found in low-HBD-3-expression 
      group. Transcriptome sequencing found that 21 genes were significantly expressed, 
      of which the function was enriched in response to bacterial origin and TNF signal 
      pathway. Vitamin D(3) could significantly up-regulate the expression of HBD-2 and 
      HBD-3, which could be controlled by knocking down CYP27A1 mRNA expression. With 
      prolonged vitamin D(3) stimulation, the expression of HBD-2 and HBD-3 increased. 
      TNF-alpha/Pg-LPS could significantly increase the expression of HBD-2, HBD-3, IL-8, 
      MCP-1, and p65, all of which were reduced by vitamin D(3) . CONCLUSION: HBDs are 
      correlated with immune infiltration in periodontitis. Vitamin D(3) inhibits the 
      expression of HBDs and chemokines induced by TNF-alpha/Pg-LPS, possibly through NF-kappaB 
      pathway, in human gingival fibroblasts.
CI  - (c) 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Zhang, Churen
AU  - Zhang C
AUID- ORCID: 0000-0001-9070-7138
AD  - Department of Stomatology, The First Affiliated Hospital of Xiamen University, 
      School of Medicine, Xiamen University, Xiamen, China.
FAU - Han, Ye
AU  - Han Y
AD  - Department of Periodontology, Peking University School and Hospital of 
      Stomatology & National Center of Stomatology & National Clinical Research Center 
      for Oral Diseases & National Engineering Laboratory for Digital and Material 
      Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & 
      Research Center of Engineering and Technology for Computerized Dentistry Ministry 
      of Health & NMPA Key Laboratory for Dental Materials, Beijing, China.
FAU - Miao, Lili
AU  - Miao L
AD  - Department of Periodontology, Peking University School and Hospital of 
      Stomatology & National Center of Stomatology & National Clinical Research Center 
      for Oral Diseases & National Engineering Laboratory for Digital and Material 
      Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & 
      Research Center of Engineering and Technology for Computerized Dentistry Ministry 
      of Health & NMPA Key Laboratory for Dental Materials, Beijing, China.
FAU - Yue, Zhaoguo
AU  - Yue Z
AD  - Department of Periodontology, Peking University School and Hospital of 
      Stomatology & National Center of Stomatology & National Clinical Research Center 
      for Oral Diseases & National Engineering Laboratory for Digital and Material 
      Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & 
      Research Center of Engineering and Technology for Computerized Dentistry Ministry 
      of Health & NMPA Key Laboratory for Dental Materials, Beijing, China.
FAU - Xu, Min
AU  - Xu M
AD  - Department of Periodontology, Peking University School and Hospital of 
      Stomatology & National Center of Stomatology & National Clinical Research Center 
      for Oral Diseases & National Engineering Laboratory for Digital and Material 
      Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & 
      Research Center of Engineering and Technology for Computerized Dentistry Ministry 
      of Health & NMPA Key Laboratory for Dental Materials, Beijing, China.
FAU - Liu, Kaining
AU  - Liu K
AUID- ORCID: 0000-0002-5762-4661
AD  - Department of Periodontology, Peking University School and Hospital of 
      Stomatology & National Center of Stomatology & National Clinical Research Center 
      for Oral Diseases & National Engineering Laboratory for Digital and Material 
      Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & 
      Research Center of Engineering and Technology for Computerized Dentistry Ministry 
      of Health & NMPA Key Laboratory for Dental Materials, Beijing, China.
FAU - Hou, Jianxia
AU  - Hou J
AUID- ORCID: 0000-0003-2414-0895
AD  - Department of Periodontology, Peking University School and Hospital of 
      Stomatology & National Center of Stomatology & National Clinical Research Center 
      for Oral Diseases & National Engineering Laboratory for Digital and Material 
      Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & 
      Research Center of Engineering and Technology for Computerized Dentistry Ministry 
      of Health & NMPA Key Laboratory for Dental Materials, Beijing, China.
LA  - eng
GR  - Beijing Natural Science Foundation (7212136)/
GR  - Fujian provincial health technology project (3502Z20224ZD1032, 3502Z20227091)/
GR  - National Natural Science Foundations of China (82071117, 81470738 and 81100749)/
GR  - Natural Science Foundations of Fujian province, China (2022J05313)/
PT  - Journal Article
DEP - 20230713
PL  - United States
TA  - J Periodontal Res
JT  - Journal of periodontal research
JID - 0055107
RN  - 0 (beta-Defensins)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1406-16-2 (Vitamin D)
SB  - IM
MH  - Humans
MH  - *beta-Defensins/genetics/metabolism
MH  - Interleukin-8/metabolism
MH  - NF-kappa B/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - *Periodontitis/metabolism
MH  - Gingiva/metabolism
MH  - Porphyromonas gingivalis/metabolism
MH  - Vitamin D
OTO - NOTNLM
OT  - bioinformatic analysis
OT  - gingival fibroblasts
OT  - immune infiltration
OT  - transcriptome sequencing
OT  - vitamin D
OT  - beta-defensins
EDAT- 2023/07/13 06:42
MHDA- 2023/09/11 06:43
CRDT- 2023/07/13 05:35
PHST- 2023/06/19 00:00 [revised]
PHST- 2022/10/11 00:00 [received]
PHST- 2023/06/30 00:00 [accepted]
PHST- 2023/09/11 06:43 [medline]
PHST- 2023/07/13 06:42 [pubmed]
PHST- 2023/07/13 05:35 [entrez]
AID - 10.1111/jre.13159 [doi]
PST - ppublish
SO  - J Periodontal Res. 2023 Oct;58(5):986-996. doi: 10.1111/jre.13159. Epub 2023 Jul 
      13.