Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia
Abstract
:1. Introduction
2. Results
2.1. Effect of Antibiotics on Expression of the CAMP Gene Encoding LL-37 in HT-29, a Colonic Epithelial Cell Line
2.2. Effect of Ciprofloxacin and Pivmecillinam on the Expression of LL-37 Peptide and Its Proform hCAP18 in HT-29 Cells
2.3. In Vivo Effect of Ciprofloxacin and Pivmecillinam on Cathelicidin Expression in Colonic Epithelia
2.4. Effect of Ciprofloxacin on the Butyrate-Induced Expression of Human β-Defensins (HBD) Transcripts in HT-29 Cells
2.5. Suppressive Effect of Ciprofloxacin on Genome-Wide Expression Profile of NaB-Induced Genes in HT-29 Cells
Entrez gene ID | Gene symbol | Description | Upregulation (NaB vs. unstimulated) | Downregulation (NaB + Cip vs. NaB) | ||
---|---|---|---|---|---|---|
Fold change | p-value | Fold change | p-value | |||
2840 | GPR17 | G protein-coupled receptor 17 | 4.37 | 0.0002 | −2.93 | 0.0013 |
84,873 | GPR128 | G protein-coupled receptor 128 | 2.7 | 0.0098 | −3.4 | 0.006 |
3816 | KLK1 | kallikrein 1 | 2.6 | 0.0012 | −1.99 | 0.014 |
6035 | RNASE1 | ribonuclease, RNase A family, 1 (pancreatic) | 8.57 | 0.0011 | −1.91 | 0.042 |
6274 | S100A3 | S100 calcium binding protein A3 | 10.54 | 0.00005 | −3.02 | 0.016 |
6271 | S100A1 | S100 calcium binding protein A1 | 7.72 | 0.0073 | −2.47 | 0.027 |
57,402 | S100A14 | S100 calcium binding protein A14 | 2.59 | 0.0056 | −1.95 | 0.015 |
4846 | NOS3 | nitric oxide synthase 3 (endothelial cell) | 4.05 | 0.0002 | −3.88 | 0.0008 |
143,662 | MUC15 | mucin 15, cell surface associated | 17.2 | 0.03 | −4.7 | 0.05 |
394,263 | MUC21 | mucin 21, cell surface associated | 3.27 | 0.0024 | −2.2 | 0.01 |
3606 | IL18 | interleukin 18 (interferon-gamma-inducing factor) | 2.93 | 0.0013 | −14.3 | 0.0003 |
400,935 | IL17REL | interleukin 17 receptor E-like | 2.57 | 0.0052 | −1.96 | 0.011 |
3554 | IL1R1 | interleukin 1 receptor, type I | 6.32 | 0.0071 | −3.26 | 0.013 |
3557 | IL1RN | interleukin 1 receptor antagonist | 3.4 | 0.02 | −3.2 | 0.04 |
2.6. Epigenetic Modifications are Involved in the Suppressive Effect of Ciprofloxacin in HT-29 Cells
2.7. In Vitro Effect of Synthetic LL-37 Peptide on C. Difficile
3. Discussion
4. Experimental
4.1. Ethics Statement
4.2. Peptides, Antibodies, Antibiotics and Sodium Butyrate
4.3. Cell Line and Growth Conditions
4.4. Primers
4.5. Bacterial Strains
4.6. Stimulation of Cells
4.7. Real-Time RT-PCR
4.8. Microarray Analysis
4.9. Cell Lysis and Histone Extraction
4.10. Western Blot Analysis
4.11. Immunofluorescence Staining of Phosphorylated Histone H3 at Ser10
4.12. Rabbit Model
4.13. In Situ Immunohistochemical Staining and Quantification of CAP-18 Peptide/Protein Expression in Rectal Mucosa of Rabbits
4.14. In Vitro Bacterial Killing
4.15. Statistical Analyses
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Sarker, P.; Mily, A.; Mamun, A.A.; Jalal, S.; Bergman, P.; Raqib, R.; Gudmundsson, G.H.; Agerberth, B. Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia. Antibiotics 2014, 3, 353-374. https://doi.org/10.3390/antibiotics3030353
Sarker P, Mily A, Mamun AA, Jalal S, Bergman P, Raqib R, Gudmundsson GH, Agerberth B. Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia. Antibiotics. 2014; 3(3):353-374. https://doi.org/10.3390/antibiotics3030353
Chicago/Turabian StyleSarker, Protim, Akhirunnesa Mily, Abdullah Al Mamun, Shah Jalal, Peter Bergman, Rubhana Raqib, Gudmundur H. Gudmundsson, and Birgitta Agerberth. 2014. "Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia" Antibiotics 3, no. 3: 353-374. https://doi.org/10.3390/antibiotics3030353