PMID- 35837068
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1792-1015 (Electronic)
IS  - 1792-0981 (Print)
IS  - 1792-0981 (Linking)
VI  - 24
IP  - 2
DP  - 2022 Aug
TI  - The complement C3a-C3aR and C5a-C5aR pathways promote viability and inflammation 
      of human retinal pigment epithelium cells by targeting NF-kappaB signaling.
PG  - 493
LID - 10.3892/etm.2022.11420 [doi]
LID - 493
AB  - Retinal detachment (RD) and its special form of rhegmatogenous RD associated with 
      choroidal detachment (RRDCD) feature similar pathological alterations, including 
      enhanced retinal cell inflammation. Although the importance of the complement 
      components C3a and C5a and their corresponding receptors in retinal maintenance 
      has been demonstrated, the relevance of these molecules to the pathogenesis of RD 
      or RRDCD remains to be investigated. The contents of C3a, C5a and inflammatory 
      factors, such as TNF-alpha, IL-1beta, IL-6 and prostaglandin (PG)E2, in related clinical 
      samples were examined by ELISA. Subsequently, human retinal pigment epithelial 
      (HRPE) cells were subjected to challenge with the C3a and C5a recombinant 
      proteins with or without C3a and C5a antagonists and NF-kappaB inhibitor, and the 
      cell viability and inflammatory cytokines were then determined by a Cell Counting 
      Kit-8 assay and ELISA, respectively. In addition, reverse 
      transcription-quantitative PCR and western blot analyses were utilized to examine 
      the mRNA or/and protein levels of C3a and its receptor C3aR, as well as C5a and 
      its receptor C5aR, and NF-kappaB. In addition, the correlation of C3a and C5a with 
      the aforementioned inflammatory factors was analyzed. The inflammatory factor 
      levels of C3a and C5a were considerably elevated in patients with RRDCD compared 
      to those in the controls. Consistently, C3a and C5a treatment led to increased 
      cell viability and aggravated inflammation in HRPE cells. Accordingly, C3a and 
      C5a induced upregulation of their corresponding receptors C3aR and C5aR, which 
      was in turn observed to be linked to the activation of the NF-kappaB signaling 
      pathway. Furthermore, there was a positive correlation of the complements C3a and 
      C5a with individual TNF-alpha, IL-1beta, IL-6 and PGE2. Taken together, the C3a-C3aR and 
      C5a-C5aR pathways were indicated to promote cell viability and inflammation of 
      HRPE cells by targeting the NF-kappaB signaling pathway.
CI  - Copyright: (c) Luo et al.
FAU - Luo, Shasha
AU  - Luo S
AD  - Department of Ophthalmology, Nanjing Medical University Affiliated Wuxi Second 
      Hospital, Wuxi, Jiangsu 214002, P.R. China.
AD  - Department of Ophthalmology, Affiliated Wuxi Clinical College of Nantong 
      University, Wuxi, Jiangsu 214002, P.R. China.
FAU - Xu, Huiyan
AU  - Xu H
AD  - Department of Ophthalmology, Nanjing Medical University Affiliated Wuxi Second 
      Hospital, Wuxi, Jiangsu 214002, P.R. China.
AD  - Department of Ophthalmology, Affiliated Wuxi Clinical College of Nantong 
      University, Wuxi, Jiangsu 214002, P.R. China.
FAU - Gong, Xuechun
AU  - Gong X
AD  - Department of Ophthalmology, Nanjing Medical University Affiliated Wuxi Second 
      Hospital, Wuxi, Jiangsu 214002, P.R. China.
FAU - Shen, Jinyan
AU  - Shen J
AD  - Department of Ophthalmology, Nanjing Medical University Affiliated Wuxi Second 
      Hospital, Wuxi, Jiangsu 214002, P.R. China.
FAU - Chen, Xuan
AU  - Chen X
AD  - Department of Ophthalmology, Nanjing Medical University Affiliated Wuxi Second 
      Hospital, Wuxi, Jiangsu 214002, P.R. China.
FAU - Wu, Zhifeng
AU  - Wu Z
AD  - Department of Ophthalmology, Nanjing Medical University Affiliated Wuxi Second 
      Hospital, Wuxi, Jiangsu 214002, P.R. China.
AD  - Department of Ophthalmology, Affiliated Wuxi Clinical College of Nantong 
      University, Wuxi, Jiangsu 214002, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20220607
PL  - Greece
TA  - Exp Ther Med
JT  - Experimental and therapeutic medicine
JID - 101531947
PMC - PMC9257899
OTO - NOTNLM
OT  - C3a-C3aR
OT  - C5a-C5aR
OT  - NF-kappaB signaling
OT  - cell viability
OT  - human retinal pigment epithelial cells
OT  - inflammation
COIS- The authors declare that they have no competing interests.
EDAT- 2022/07/16 06:00
MHDA- 2022/07/16 06:01
PMCR- 2022/06/07
CRDT- 2022/07/15 02:34
PHST- 2022/02/10 00:00 [received]
PHST- 2022/04/08 00:00 [accepted]
PHST- 2022/07/15 02:34 [entrez]
PHST- 2022/07/16 06:00 [pubmed]
PHST- 2022/07/16 06:01 [medline]
PHST- 2022/06/07 00:00 [pmc-release]
AID - ETM-24-2-11420 [pii]
AID - 10.3892/etm.2022.11420 [doi]
PST - epublish
SO  - Exp Ther Med. 2022 Jun 7;24(2):493. doi: 10.3892/etm.2022.11420. eCollection 2022 
      Aug.