PMID- 34140795
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220424
IS  - 1178-7031 (Print)
IS  - 1178-7031 (Electronic)
IS  - 1178-7031 (Linking)
VI  - 14
DP  - 2021
TI  - High Inflammatory Tendency Induced by Malignant Stimulation Through Imbalance of 
      CD28 and CTLA-4/PD-1 Contributes to Dopamine Neuron Injury.
PG  - 2471-2482
LID - 10.2147/JIR.S316439 [doi]
AB  - BACKGROUND: Parkinson's disease is a common neurodegenerative disease in the 
      elderly. The incidence of various cancers in Parkinson's disease patients is 
      significantly lower than in healthy people. Parkinson's disease patients are 
      individuals with a high tendency for inflammation, whose peripheral immune system 
      is represented in an activated state. We hypothesized that the hyperinflammatory 
      predisposition of Parkinson's disease patients is pathogenic. METHODS: DBA/1 mice 
      were used to simulate "highly inflammatory individuals", and the carcinogen DEN 
      was used to induce malignancy. Hematoxylin & eosin (H&E) staining was used to 
      observe the formation of lung tumors. Apoptosis of neurons was observed by 
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) 
      staining. Immunohistochemistry and flow cytometry were used to observe CD4, CD28, 
      major histocompatibility complex II (MHCII), cytotoxic T-lymphocyte-associated 
      antigen 4 (CTLA-4), and programmed death 1 (PD-1). The ionized calcium binding 
      adaptor molecule-1 (IBA-1) + inducible nitric oxide synthase (iNOS) was used to 
      label M1 microglia, and IBA-1 + arginase 1 (Arg1) was used to label M2 microglia 
      by immunofluorescence. The expression of pro-inflammatory cytokines tumor 
      necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and anti-inflammatory 
      cytokines IL-10 and IL-4 was detected by ELISA. RESULTS: DBA/1 mice with high 
      inflammatory tendency showed a continuous increase of peripheral inflammation, 
      promoting intracranial inflammation, decreasing the tumor incidence and 
      increasing the neurodegeneration under induction of malignant change. CD28 and 
      CTLA-4/PD-1 reduced the T-cell-dominated inflammatory response, reduced the 
      intracerebral inflammatory response, protected from neurodegeneration, and 
      increased the incidence of tumor. Combination of CTLA-4 and PD-1 blocker can 
      overactivate T cells, worsen peripheral and intracranial inflammation, reduce the 
      incidence of tumor, cause damage to dopamine neurons, and promote the occurrence 
      of neurodegeneration. CONCLUSION: High inflammatory tendency induced by malignant 
      stimulation through the imbalance of CD28 and CTLA-4/PD-1 leads to dopamine 
      neuron injury.
CI  - (c) 2021 Dong et al.
FAU - Dong, Li
AU  - Dong L
AD  - Department of Neurology, The Fourth Affiliated Hospital of China Medical 
      University, Shenyang, People's Republic of China.
FAU - Zheng, Yu-Min
AU  - Zheng YM
AD  - Department of Neurology, The First Affiliated Hospital of China Medical 
      University, Shenyang, People's Republic of China.
FAU - Luo, Xiao-Guang
AU  - Luo XG
AD  - Department of Neurology, The First Affiliated Hospital of South University of 
      Science and Technology, The Second Clinical College of Jinan University, Shenzhen 
      People's Hospital, Shenzhen, People's Republic of China.
FAU - He, Zhi-Yi
AU  - He ZY
AD  - Department of Neurology, The First Affiliated Hospital of China Medical 
      University, Shenyang, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20210610
PL  - New Zealand
TA  - J Inflamm Res
JT  - Journal of inflammation research
JID - 101512684
PMC - PMC8203269
OTO - NOTNLM
OT  - CD28
OT  - CTLA-4/PD-1
OT  - dopamine neuron injury
OT  - high inflammatory tendency
OT  - malignant stimulation
COIS- The authors declare that they have no competing interests.
EDAT- 2021/06/19 06:00
MHDA- 2021/06/19 06:01
PMCR- 2021/06/10
CRDT- 2021/06/18 06:40
PHST- 2021/04/19 00:00 [received]
PHST- 2021/05/24 00:00 [accepted]
PHST- 2021/06/18 06:40 [entrez]
PHST- 2021/06/19 06:00 [pubmed]
PHST- 2021/06/19 06:01 [medline]
PHST- 2021/06/10 00:00 [pmc-release]
AID - 316439 [pii]
AID - 10.2147/JIR.S316439 [doi]
PST - epublish
SO  - J Inflamm Res. 2021 Jun 10;14:2471-2482. doi: 10.2147/JIR.S316439. eCollection 
      2021.