Open AccessBacterial exotoxins downregulate cathelicidin (hCAP‐18/LL‐37) and human β‐defensin 1 (HBD‐1) expression in the intestinal epithelial cells
Author(s) -
Chakraborty Krishnendu,
Ghosh Shubhamoy,
Koley Hemanta,
Mukhopadhyay Asish Kumar,
Ramamurthy Thandavarayan,
Saha Dhira Rani,
Mukhopadhyay Debashis,
Roychowdhury Swasti,
Hamabata Takashi,
Takeda Yoshifumi,
Das Santasabuj
Publication year - 2008
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2008.01227.x
Subject(s) - biology , microbiology and biotechnology , vibrio cholerae , cholera toxin , cathelicidin , virulence , downregulation and upregulation , antimicrobial peptides , beta defensin , defensin , mapk/erk pathway , signal transduction , antimicrobial , gene , bacteria , biochemistry , genetics
Summary Cathelicidin (hCAP‐18/LL‐37) and β‐defensin 1 (HBD‐1) are human antimicrobial peptides (AMPs) with high basal expression levels, which form the first line of host defence against infections over the epithelial surfaces. The antimicrobial functions owe to their direct microbicidal effects as well as the immunomodulatory role. Pathogenic microorganisms have developed multiple modalities including transcriptional repression to combat this arm of the host immune response. The precise mechanisms and the pathogen‐derived molecules responsible for transcriptional downregulation remain unknown. Here, we have shown that enteric pathogens suppress LL‐37 and HBD‐1 expression in the intestinal epithelial cells (IECs) with Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) exerting the most dramatic effects. Cholera toxin (CT) and labile toxin (LT), the major virulence proteins of V. cholerae and ETEC, respectively, are predominantly responsible for these effects, both in vitro and in vivo . CT transcriptionally downregulates the AMPs by activating several intracellular signalling pathways involving protein kinase A (PKA), ERK MAPKinase and Cox‐2 downstream of cAMP accumulation and inducible cAMP early repressor (ICER) may mediate this role of CT, at least in part. This is the first report to show transcriptional repression of the AMPs through the activation of cellular signal transduction pathways by well‐known virulence proteins of pathogenic microorganisms.