Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia
Antibiotics exert several effects on host cells including regulation of immune components. Antimicrobial peptides (AMPs), e.g., cathelicidins and defensins display multiple functions in innate immunity. In colonic mucosa, cathelicidins are induced by butyrate, a bacterial fermentation product. Here,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2014-07-01
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| Series: | Antibiotics |
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| Online Access: | http://www.mdpi.com/2079-6382/3/3/353 |
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| author | Protim Sarker Akhirunnesa Mily Abdullah Al Mamun Shah Jalal Peter Bergman Rubhana Raqib Gudmundur H. Gudmundsson Birgitta Agerberth |
| author_facet | Protim Sarker Akhirunnesa Mily Abdullah Al Mamun Shah Jalal Peter Bergman Rubhana Raqib Gudmundur H. Gudmundsson Birgitta Agerberth |
| author_sort | Protim Sarker |
| collection | DOAJ |
| description | Antibiotics exert several effects on host cells including regulation of immune components. Antimicrobial peptides (AMPs), e.g., cathelicidins and defensins display multiple functions in innate immunity. In colonic mucosa, cathelicidins are induced by butyrate, a bacterial fermentation product. Here, we investigated the effect of antibiotics on butyrate-induced expression of cathelicidins and beta-defensins in colon epithelial cells. Real-time PCR analysis revealed that ciprofloxacin and clindamycin reduce butyrate-induced transcription of the human cathelicidin LL-37 in the colonic epithelial cell line HT-29. Suppression of LL-37 peptide/protein by ciprofloxacin was confirmed by Western blot analysis. Immunohistochemical analysis demonstrated that ciprofloxacin suppresses the rabbit cathelicidin CAP-18 in rectal epithelia of healthy and butyrate-treated Shigella-infected rabbits. Ciprofloxacin also down-regulated butyrate-induced transcription of the human beta-defensin-3 in HT-29 cells. Microarray analysis of HT-29 cells revealed upregulation by butyrate with subsequent down-regulation by ciprofloxacin of additional genes encoding immune factors. Dephosphorylation of histone H3, an epigenetic event provided a possible mechanism of the suppressive effect of ciprofloxacin. Furthermore, LL-37 peptide inhibited Clostridium difficile growth in vitro. In conclusion, ciprofloxacin and clindamycin exert immunomodulatory function by down-regulating AMPs and other immune components in colonic epithelial cells. Suppression of AMPs may contribute to the overgrowth of C. difficile, causing antibiotic-associated diarrhea. |
| first_indexed | 2024-12-23T11:49:04Z |
| format | Article |
| id | doaj.art-219adfcfa308408987771a7adb6addde |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-12-23T11:49:04Z |
| publishDate | 2014-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-219adfcfa308408987771a7adb6addde2022-12-21T17:48:14ZengMDPI AGAntibiotics2079-63822014-07-013335337410.3390/antibiotics3030353antibiotics3030353Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon EpitheliaProtim Sarker0Akhirunnesa Mily1Abdullah Al Mamun2Shah Jalal3Peter Bergman4Rubhana Raqib5Gudmundur H. Gudmundsson6Birgitta Agerberth7Centre for Vaccine Science, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212, BangladeshCentre for Vaccine Science, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212, BangladeshCentre for Vaccine Science, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212, BangladeshDepartment of Laboratory Medicine, Division of Clinical Microbiology (F68), Karolinska University Hospital Huddinge, S-141 86 Stockholm, SwedenDepartment of Laboratory Medicine, Division of Clinical Microbiology (F68), Karolinska University Hospital Huddinge, S-141 86 Stockholm, SwedenCentre for Vaccine Science, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212, BangladeshInstitute of Biology and Biomedical Center, University of Iceland, 101 Reykjavik, IcelandDepartment of Laboratory Medicine, Division of Clinical Microbiology (F68), Karolinska University Hospital Huddinge, S-141 86 Stockholm, SwedenAntibiotics exert several effects on host cells including regulation of immune components. Antimicrobial peptides (AMPs), e.g., cathelicidins and defensins display multiple functions in innate immunity. In colonic mucosa, cathelicidins are induced by butyrate, a bacterial fermentation product. Here, we investigated the effect of antibiotics on butyrate-induced expression of cathelicidins and beta-defensins in colon epithelial cells. Real-time PCR analysis revealed that ciprofloxacin and clindamycin reduce butyrate-induced transcription of the human cathelicidin LL-37 in the colonic epithelial cell line HT-29. Suppression of LL-37 peptide/protein by ciprofloxacin was confirmed by Western blot analysis. Immunohistochemical analysis demonstrated that ciprofloxacin suppresses the rabbit cathelicidin CAP-18 in rectal epithelia of healthy and butyrate-treated Shigella-infected rabbits. Ciprofloxacin also down-regulated butyrate-induced transcription of the human beta-defensin-3 in HT-29 cells. Microarray analysis of HT-29 cells revealed upregulation by butyrate with subsequent down-regulation by ciprofloxacin of additional genes encoding immune factors. Dephosphorylation of histone H3, an epigenetic event provided a possible mechanism of the suppressive effect of ciprofloxacin. Furthermore, LL-37 peptide inhibited Clostridium difficile growth in vitro. In conclusion, ciprofloxacin and clindamycin exert immunomodulatory function by down-regulating AMPs and other immune components in colonic epithelial cells. Suppression of AMPs may contribute to the overgrowth of C. difficile, causing antibiotic-associated diarrhea.http://www.mdpi.com/2079-6382/3/3/353antibiobicmicrobiotabutyratehistone modificationshost defense peptidesLL-37innate immunity impaired immune responsesClostridium difficileantibiotic-associated diarrhea |
| spellingShingle | Protim Sarker Akhirunnesa Mily Abdullah Al Mamun Shah Jalal Peter Bergman Rubhana Raqib Gudmundur H. Gudmundsson Birgitta Agerberth Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia Antibiotics antibiobic microbiota butyrate histone modifications host defense peptides LL-37 innate immunity impaired immune responses Clostridium difficile antibiotic-associated diarrhea |
| title | Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia |
| title_full | Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia |
| title_fullStr | Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia |
| title_full_unstemmed | Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia |
| title_short | Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia |
| title_sort | ciprofloxacin affects host cells by suppressing expression of the endogenous antimicrobial peptides cathelicidins and beta defensin 3 in colon epithelia |
| topic | antibiobic microbiota butyrate histone modifications host defense peptides LL-37 innate immunity impaired immune responses Clostridium difficile antibiotic-associated diarrhea |
| url | http://www.mdpi.com/2079-6382/3/3/353 |
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