PMID- 38284254
OWN - NLM
STAT- MEDLINE
DCOM- 20240130
LR  - 20240301
IS  - 1007-8738 (Print)
IS  - 1007-8738 (Linking)
VI  - 40
IP  - 2
DP  - 2024 Feb
TI  - [High mobility group nucleosome binding protein 1 (HMGN1) induces activation of 
      mouse BV2 microglia and upregulates their pro-inflammatory mediator expression by 
      activating TLR4/MyD88/NF-kappaB p65/IKK-beta signal pathway].
PG  - 135-141
AB  - Objective To explore the effects and mechanism of high-mobility group 
      nucleosome-binding protein 1 (HMGN1) on the inflammatory response of mouse BV2 
      microglia. Methods BV2 cells were incubated with recombinant HMGN1 at different 
      concentrations (0, 100, 200, 500, 1000, 2000 ng/mL) for 6 hours, and the 
      morphological changes were observed under a microscope. The mRNA levels of tumor 
      necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1beta (IL-1beta) and 
      monocyte chemotactic protein 1 (MCP-1) were detected by real time quantitative 
      PCR. Microglial cells were then randomly divided into a control group, model 
      group, inhibitor group and antagonist group. The cells in the model group were 
      treated with 500 ng/mL HMGN1, while the antagonist group was treated with 500 
      ng/mL TAK-242 (resatorvid), a Toll-like receptor 4 (TLR4) antagonist, in addition 
      to HMGN1. Real time quantitative PCR and immunofluorescence were used to detect 
      the expression of M1/M2 markers in the four groups, and Western blot analysis was 
      used to measure the protein expression levels of inducible nitric-oxide synthase 
      (iNOS), TLR4, myeloid differentiation factor88 (MyD88), nuclear factor kappaB p65 
      (NF-kappaB p65) and inhibitor of NF-kappaB(IkappaB)kinase beta(IKK-beta). Results After the 
      treatment of HMGN1, the morphology of BV2 cells changed significantly, showing an 
      amoeba-like appearance. The mRNA levels of TNF-alpha, IL-6, IL-1beta and MCP-1 increased 
      with the HMGN1 concentration, with a statistically significant difference 
      compared to the 0 ng/mL HMGN1 group. At the same time, the mRNA level of iNOS, a 
      M1 phenotype marker, increased with the HMGN1 concentration, while the level of 
      CD206, a M2 phenotype marker, decreased with HMGN1 concentration, showing a 
      statistically significant difference compared to the 0 ng/mL HMGN1 group. 
      Compared with the model group, the mRNA level of M1 phenotypic marker iNOS in the 
      antagonist group was significantly lower, and the level of M2 phenotypic marker 
      CD206 was significantly higher. The results of immunofluorescence cytochemistry 
      also showed that the expression of M1 phenotypic marker iNOS in the antagonist 
      group was lower. The results of Western blot suggested that the protein 
      expression levels of iNOS, TLR4, MyD88, NF-kappaB p65 and IKK-beta decreased 
      significantly in the antagonist group. Conclusion HMGN1 may induce the activation 
      of BV2 microglial cells by upregulating pro-inflammatory mediators through 
      activating the TLR4/MyD88/NF-kappaB p65/IKK-beta signaling pathway.
FAU - Mao, Yan
AU  - Mao Y
AD  - Department of Nephrology, Guizhou Provincial People's Hospital, Guiyang 550002; 
      School of Medicine, Guizhou University, Guiyang 550025, China.
FAU - Yu, Jiali
AU  - Yu J
AD  - Department of Nephrology, Guizhou Provincial People's Hospital, Guiyang 550002; 
      School of Medicine, Guizhou University, Guiyang 550025; NHC Key Laboratory of 
      Pulmonary Immunological Disease, Guizhou Provincial People's Hospital, Guiyang 
      550002, China.
FAU - Yuan, Jing
AU  - Yuan J
AD  - Department of Nephrology, Guizhou Provincial People's Hospital, Guiyang 550002; 
      School of Medicine, Guizhou University, Guiyang 550025; NHC Key Laboratory of 
      Pulmonary Immunological Disease, Guizhou Provincial People's Hospital, Guiyang 
      550002, China.
FAU - DA, Jingjing
AU  - DA J
AD  - Department of Nephrology, Guizhou Provincial People's Hospital, Guiyang 550002; 
      School of Medicine, Guizhou University, Guiyang 550025; NHC Key Laboratory of 
      Pulmonary Immunological Disease, Guizhou Provincial People's Hospital, Guiyang 
      550002, China.
FAU - Yu, Fuxun
AU  - Yu F
AD  - Department of Nephrology, Guizhou Provincial People's Hospital, Guiyang 550002; 
      School of Medicine, Guizhou University, Guiyang 550025; NHC Key Laboratory of 
      Pulmonary Immunological Disease, Guizhou Provincial People's Hospital, Guiyang 
      550002, China.
FAU - Zha, Yan
AU  - Zha Y
AD  - Department of Nephrology, Guizhou Provincial People's Hospital, Guiyang 550002; 
      School of Medicine, Guizhou University, Guiyang 550025; NHC Key Laboratory of 
      Pulmonary Immunological Disease, Guizhou Provincial People's Hospital, Guiyang 
      550002, China. *Corresponding author, E-mail: zhayan72@126.com.
LA  - chi
PT  - English Abstract
PT  - Journal Article
PL  - China
TA  - Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
JT  - Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular 
      immunology
JID - 101139110
RN  - 0 (HMGN1 Protein)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-6)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (Nucleosomes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *HMGN1 Protein/genetics/metabolism
MH  - Inflammation Mediators/metabolism
MH  - Interleukin-6/metabolism
MH  - Microglia
MH  - Myeloid Differentiation Factor 88/genetics
MH  - *NF-kappa B/metabolism
MH  - Nucleosomes/metabolism
MH  - RNA, Messenger/metabolism
MH  - Signal Transduction
MH  - Toll-Like Receptor 4/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2024/01/29 06:43
MHDA- 2024/01/30 12:43
CRDT- 2024/01/29 05:29
PHST- 2024/01/30 12:43 [medline]
PHST- 2024/01/29 06:43 [pubmed]
PHST- 2024/01/29 05:29 [entrez]
PST - ppublish
SO  - Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2024 Feb;40(2):135-141.