Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia

Antibiotics

Protim Sarker¹  Akhirunnesa Mily¹  Abdullah Al Mamun¹  Shah Jalal³  Peter Bergman³  Rubhana Raqib¹  Gudmundur H. Gudmundsson² 

[1] Centre for Vaccine Science, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka 1212, Bangladesh; E-Mails:;Institute of Biology and Biomedical Center, University of Iceland, 101 Reykjavik, Iceland; E-Mail:;Department of Laboratory Medicine, Division of Clinical Microbiology (F68), Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden; E-Mails:

关键词: antibiobic;    microbiota;    butyrate;    histone modifications;    host defense peptides;    LL-37;    innate immunity;    impaired immune responses;    Clostridium difficile;    antibiotic-associated diarrhea;   

DOI  :  10.3390/antibiotics3030353

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.