PMID- 31115023
OWN - NLM
STAT- MEDLINE
DCOM- 20200908
LR  - 20200908
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 23
IP  - 9
DP  - 2019 May
TI  - A study of regulatory effects of TLR4 and NF-kappaB on primary biliary cholangitis.
PG  - 3951-3959
LID - 17824 [pii]
LID - 10.26355/eurrev_201905_17824 [doi]
AB  - OBJECTIVE: To investigate the regulatory effects of the Toll-like receptor 4 
      (TLR4) and the nuclear factor kappa-light-chain-enhancer of the activated B cells 
      (NF-kappaB) on primary biliary cholangitis (PBC) and to analyze the possible 
      mechanisms. MATERIALS AND METHODS: A total of 24 C57BL/6 mice were randomly 
      divided into M group (n=12, intraperitoneally injected with polyinosinic 
      acid-polycytidine acid (PolyI:C) for 12 consecutive weeks, 2 times/week) and C 
      group (n=12, intraperitoneally injected with the same volume of normal saline). 
      After 12 weeks, the mice were sacrificed to collect liver tissues. Then, an 
      enzyme-linked immunosorbent assay (ELISA) kit was used to detect the content of 
      interleukin-6 (IL-6), IL-10, and tumor necrosis factor-alpha (TNF-alpha) in liver 
      tissues. Hematoxylin-eosin (HE) staining assay was performed to observe the 
      pathological changes of liver tissues, and measure the levels of alanine 
      aminotransferase (ALT) and aspartate aminotransferase (AST) in peripheral blood 
      of mice. Terminal deoxynucleotidyl transferase-mediated deoxyuridine 
      triphosphate-biotin nick end-labeling (TUNEL) staining was applied to determine 
      cell apoptosis in liver tissues. The relative messenger ribonucleic acid (mRNA) 
      expression levels of TLR4 and NF-kappaB in liver tissues were detected by 
      quantitative Polymerase Chain Reaction (qPCR). Western blotting was adopted to 
      measure the protein expressions of TLR4, NF-kappaB, myeloid differentiation factor 88 
      (MyD88), B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax), and 
      Caspase-3. RESULTS: Compared with that in C group, the content of IL-6 and TNF-alpha 
      in liver tissues in M group was significantly increased (p<0.01), but the level 
      of IL-10 was statistically downregulated (p<0.01). According to HE staining, 
      liver damage of mice in M group was evidently severer than that in C group, and 
      the levels of ALT and AST in M group were significantly higher than those in C 
      group (p<0.01). The amount of TUNEL-positive cells in liver tissues in M group 
      was significantly greater than that in C group (p<0.01). The levels of TLR4 and 
      NF-kappaB mRNA in liver tissues from M group were significantly elevated in 
      comparison with the C group (p<0.01). Compared with those in C group, the 
      expressions of TLR4, NF-kappaB, MyD88, and Caspase-3 proteins in M group showed 
      statistical increases in liver tissues (p<0.01), whereas that of Bcl-2/Bax was 
      significantly declined (p<0.01). CONCLUSIONS: PBC activates the TLR4/MyD88/NF-kappaB 
      signaling pathway, induces the release of inflammatory factors and produces a 
      large number of apoptotic proteins, which results in liver damage and cell 
      apoptosis in mice.
FAU - Yu, Y
AU  - Yu Y
AD  - Jinan University, Guangzhou, Guangdong, China. YuanYu2fw@163.com.
FAU - Li, M-P
AU  - Li MP
FAU - Xu, B
AU  - Xu B
FAU - Fan, F
AU  - Fan F
FAU - Lu, S-F
AU  - Lu SF
FAU - Pan, M
AU  - Pan M
FAU - Wu, H-S
AU  - Wu HS
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Interleukin-6)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Alanine Transaminase/blood
MH  - Animals
MH  - Aspartate Aminotransferases/blood
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression Regulation
MH  - Interleukin-10/metabolism
MH  - Interleukin-6/metabolism
MH  - Liver/metabolism/pathology
MH  - Liver Cirrhosis, Biliary/chemically induced/metabolism/*pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myeloid Differentiation Factor 88/metabolism
MH  - NF-kappa B/genetics/*metabolism
MH  - Poly I-C/toxicity
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Signal Transduction
MH  - Toll-Like Receptor 4/genetics/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - bcl-2-Associated X Protein/metabolism
EDAT- 2019/05/23 06:00
MHDA- 2020/09/09 06:00
CRDT- 2019/05/23 06:00
PHST- 2019/05/23 06:00 [entrez]
PHST- 2019/05/23 06:00 [pubmed]
PHST- 2020/09/09 06:00 [medline]
AID - 17824 [pii]
AID - 10.26355/eurrev_201905_17824 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2019 May;23(9):3951-3959. doi: 
      10.26355/eurrev_201905_17824.