title: Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia.
abstract: 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.
authors.affiliation: Centre for Vaccine Science, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212, Bangladesh. protim@icddrb.org.
authors.forename: Protim
authors.initials: P
authors.lastname: Sarker
authors.affiliation: Centre for Vaccine Science, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212, Bangladesh. mily@icddrb.org.
authors.forename: Akhirunnesa
authors.initials: A
authors.lastname: Mily
authors.affiliation: Centre for Vaccine Science, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212, Bangladesh. mamun104@gmail.com.
authors.forename: Abdullah Al
authors.initials: AA
authors.lastname: Mamun
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Microbiology (F68), Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden. Shah.Jalal@ki.se.
authors.forename: Shah
authors.initials: S
authors.lastname: Jalal
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Microbiology (F68), Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden. Peter.Bergman@ki.se.
authors.forename: Peter
authors.initials: P
authors.lastname: Bergman
authors.affiliation: Centre for Vaccine Science, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212, Bangladesh. rubhana@icddrb.org.
authors.forename: Rubhana
authors.initials: R
authors.lastname: Raqib
authors.affiliation: Institute of Biology and Biomedical Center, University of Iceland, 101 Reykjavik, Iceland. ghrafn@hi.is.
authors.forename: Gudmundur H
authors.initials: GH
authors.lastname: Gudmundsson
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Microbiology (F68), Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden. Birgitta.Agerberth@ki.se.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Agerberth
keywords: Clostridium difficile; LL-37; antibiobic; antibiotic-associated diarrhea; butyrate; histone modifications; host defense  peptides; impaired immune responses; innate immunity; microbiota