Properdin Modulates Complement Component Production in Stressed Human Primary Retinal Pigment Epithelium Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cultivation and Treatment of hpRPE
2.2. hpRPE Genotyping
2.3. RT-qPCR and PCR
2.4. Multiplex Complement Secretion Assay
2.5. Western Blot
2.6. Immunohistochemistry
2.7. Statistics
3. Results
3.1. Human Primary RPE Cells as a Model System in Cell Culture
3.2. hpRPE Cells Produce Complement Components
3.3. AMD-Risk SNPs in Complement Genes Increase hpRPE Cell-Dependent Complement Secretion
3.4. Complement Regulator Properdin Increased Expression of Complement Proteases in Stressed hpRPE Cells
3.5. Inflammasome-Associated Transcription Levels were Reduced by Properdin in Stressed hpRPE Cells
4. Discussion
4.1. Biological Relevance of hpRPE In Vitro Experiments
4.2. hpRPE as a Source for Complement Components in the Eye
4.3. AMD-Risk SNPs in Complement Genes Enhanced hpRPE Cell-Dependent Complement Secretion
4.4. hpRPE Cell-Dependent Complement Activation
4.5. Oxidative Stress and Properdin Altered Complement and Inflammasome Associated Expression in hpRPE Cells
4.6. Time-Dependent Shift in Complement Gene Expression Levels Following Properdin Treatment of Stressed hpRPE
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Used Methods and Results Reference | protein (Fig. 1B) | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
mRNA (Fig. 1A, 3, 5) | | ||||||||||||||||
secretion (Fig. 1C, 4) | secretion (Fig. 1C, 2, S2) | ||||||||||||||||
Gene Accession | RPE donors | ||||||||||||||||
Gene | Number | SNP ID | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 |
CFH | NG_007259 | rs121913059 | C | C | C | C | C | C | C | C | C | C | C | C | C | C | C |
CFH(Y402H) | NG_007259 | rs1061170 | CT | T | CT | T | C | T | CT | T | T | T | CT | T | CT | CT | CT |
CFH | NG_007259 | rs570618 | GT | G | GT | G | T | G | GT | G | G | G | GT | G | GT | GT | GT |
CFH | NG_007259 | rs10922109 | AC | A | AC | AC | C | AC | AC | AC | AC | A | AC | C | AC | AC | AC |
CFHR3/CFHR1 | NG_015993 | rs61818925 | G | GT | G | G | GT | G | GT | G | G | G | G | G | G | G | G |
C3 | NG_009557 | rs2230199 | C | C | C | C | C | C | C | C | C | C | C | C | CG | C | C |
C3 | NG_009557 | rs147859257 | T | T | T | T | T | T | T | T | T | T | T | T | T | T | T |
C2/CFB | NG_011730 | rs116503776 | G | GA | G | G | G | G | GA | G | G | G | G | GA | A | G | G |
C2/CFB | NG_011730 | rs144629244 | C | C | C | C | C | C | C | C | C | C | C | C | C | C | C |
CFI | NG_007569 | rs141853578 | C | C | C | C | C | C | C | C | C | C | C | C | C | C | C |
CFI | NG_007569 | rs10033900 | TC | T | TC | TC | T | TC | TC | TC | T | TC | TC | TC | C | TC | C |
ARMS2 | NG_011725 | rs3750846 | A | AG | AG | A | AG | A | A | AG | AG | A | AG | AG | AG | A | A |
C9 | NG_009894 | rs6235861 | G | G | G | G | G | G | G | G | G | G | G | G | G | G | G |
none AMD-risk | heterozygous | AMD-risk |
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Schäfer, N.; Wolf, H.N.; Enzbrenner, A.; Schikora, J.; Reichenthaler, M.; Enzmann, V.; Pauly, D. Properdin Modulates Complement Component Production in Stressed Human Primary Retinal Pigment Epithelium Cells. Antioxidants 2020, 9, 793. https://doi.org/10.3390/antiox9090793
Schäfer N, Wolf HN, Enzbrenner A, Schikora J, Reichenthaler M, Enzmann V, Pauly D. Properdin Modulates Complement Component Production in Stressed Human Primary Retinal Pigment Epithelium Cells. Antioxidants. 2020; 9(9):793. https://doi.org/10.3390/antiox9090793
Chicago/Turabian StyleSchäfer, Nicole, Hannah N. Wolf, Anne Enzbrenner, Juliane Schikora, Maria Reichenthaler, Volker Enzmann, and Diana Pauly. 2020. "Properdin Modulates Complement Component Production in Stressed Human Primary Retinal Pigment Epithelium Cells" Antioxidants 9, no. 9: 793. https://doi.org/10.3390/antiox9090793
APA StyleSchäfer, N., Wolf, H. N., Enzbrenner, A., Schikora, J., Reichenthaler, M., Enzmann, V., & Pauly, D. (2020). Properdin Modulates Complement Component Production in Stressed Human Primary Retinal Pigment Epithelium Cells. Antioxidants, 9(9), 793. https://doi.org/10.3390/antiox9090793