PMID- 30116631
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220318
IS  - 2090-004X (Print)
IS  - 2090-0058 (Electronic)
IS  - 2090-004X (Linking)
VI  - 2018
DP  - 2018
TI  - Inhibition of Proteasome Activity Upregulates IL-6 Expression in RPE Cells 
      through the Activation of P38 MAPKs.
PG  - 5392432
LID - 10.1155/2018/5392432 [doi]
LID - 5392432
AB  - PURPOSE: As far as we know, during the development of age-related macular 
      degeneration (AMD), the activity of proteasome in retinal pigment epithelium 
      cells (RPE) gradually decreases. And a lot of research has shown that age-related 
      macular degeneration is closely related to inflammation and autoimmune. Moreover, 
      there are many cytokines (CKs) involved in the course of inflammation. In this 
      study, we are going to investigate how the decrease of proteasome activity 
      affects the production of interleukin-6 (IL-6) in human retinal pigment 
      epithelium cells (ARPE-19). METHODS: Cultured ARPE-19 was treated with or without 
      MG132, a proteasome inhibitor, and the levels of IL-6 mRNA (messenger ribonucleic 
      acid) in RPE at 1 h, 4 h, 8 h, and IL-6 protein in the culture medium at 2 h, 
      4 h, 6 h, 8 h, 10 h, and 12 h were measured by real-time polymerase chain 
      reaction (real-time PCR) and enzyme-linked immunosorbent assay (ELISA). The 
      protein levels of MCP-1 (monocyte chemoattractant protein-1) in the culture 
      medium at 2 h, 4 h, 6 h, 8 h, 10 h, and 12 h were also measured by ELISA. Then we 
      tested which of cell signal pathways regulating the production of IL-6 were 
      activated when we added MG132 into the medium by Western blot and electrophoretic 
      mobility shift assays (EMSA). After that, we put the inhibitors of these 
      activated cell signal pathways into the medium individually to see which 
      inhibitor can counteract the effect of upregulating the levels of IL-6 in the 
      culture medium of RPE. RESULTS: MG132 decreased the secretion of MCP-1 in the 
      culture medium of RPE, but it increased the expression of IL-6 mRNA in RPE and 
      IL-6 protein level in the culture medium of RPE. MG132 treatment was also found 
      to enhance the level of phosphorylated p38 mitogen-activated protein kinases 
      (MAPKs) and c-Jun N-terminal Kinase (JNK) by Western blotting. More importantly, 
      the effect of MG132 on upregulating the levels of IL-6 was inhibited by SB203580, 
      an inhibitor of P38 MAP kinases. But the JNK inhibitor, SP600125, cannot prevent 
      the effect of upregulating the levels of IL-6 by MG132 in the RPE culture medium. 
      CONCLUSIONS: We concluded that the proteasome inhibitor, MG132, upregulates IL-6 
      production in RPE cells through the activation of P38 MAPKs.
FAU - Qin, Tingyu
AU  - Qin T
AD  - Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou 450000, China.
FAU - Gao, Shasha
AU  - Gao S
AUID- ORCID: 0000-0001-5751-7105
AD  - Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou 450000, China.
LA  - eng
PT  - Journal Article
DEP - 20180712
PL  - United States
TA  - J Ophthalmol
JT  - Journal of ophthalmology
JID - 101524199
PMC - PMC6079444
EDAT- 2018/08/18 06:00
MHDA- 2018/08/18 06:01
PMCR- 2018/07/12
CRDT- 2018/08/18 06:00
PHST- 2018/03/29 00:00 [received]
PHST- 2018/06/19 00:00 [accepted]
PHST- 2018/08/18 06:00 [entrez]
PHST- 2018/08/18 06:00 [pubmed]
PHST- 2018/08/18 06:01 [medline]
PHST- 2018/07/12 00:00 [pmc-release]
AID - 10.1155/2018/5392432 [doi]
PST - epublish
SO  - J Ophthalmol. 2018 Jul 12;2018:5392432. doi: 10.1155/2018/5392432. eCollection 
      2018.