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Thymic stromal lymphopoietin exerts antimicrobial activities.

Sonesson, Andreas LU ; Kasetty, Gopinath LU ; Olin, Anders LU ; Malmsten, Martin; Mörgelin, Matthias LU ; Sørensen, Ole E LU and Schmidtchen, Artur LU (2011) In Experimental Dermatology 20(12). p.1004-1010
Abstract
Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like cytokine expressed by epithelial cells and reported to be involved in allergic diseases and atopic eczema. The presence of several predicted α-helical regions in TSPL, a structure characterizing many classical antimicrobial peptides (AMPs), prompted us to investigate whether TSLP exerts antimicrobial activities. Recombinant human TSLP exerted antimicrobial activity, particularly against Gram-negative bacteria. Using synthetic overlapping peptide 20-mers of TSLP, it was demonstrated that the antimicrobial effect is primarily mediated by the C-terminal region of the protein. MKK34 (MKKRRKRKVTTNKCLEQVSQLQGLWRRFNRPLLK), a peptide spanning a C-terminal α-helical region in TSLP, showed... (More)
Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like cytokine expressed by epithelial cells and reported to be involved in allergic diseases and atopic eczema. The presence of several predicted α-helical regions in TSPL, a structure characterizing many classical antimicrobial peptides (AMPs), prompted us to investigate whether TSLP exerts antimicrobial activities. Recombinant human TSLP exerted antimicrobial activity, particularly against Gram-negative bacteria. Using synthetic overlapping peptide 20-mers of TSLP, it was demonstrated that the antimicrobial effect is primarily mediated by the C-terminal region of the protein. MKK34 (MKKRRKRKVTTNKCLEQVSQLQGLWRRFNRPLLK), a peptide spanning a C-terminal α-helical region in TSLP, showed potent antimicrobial activities, in physiological salt conditions and in the presence of human plasma. Fluorescent studies of peptide-treated bacteria, electron microscopy and liposome leakage models showed that MKK34 exerted membrane-disrupting effects comparable to those of the classical AMP LL-37. Moreover, TSLP was degraded into multiple fragments by staphylococcal V8 proteinase. One major antimicrobial degradation fragment was found to encompass the C-terminal antimicrobial region defined by the MKK34 peptide. We here describe a novel antimicrobial role for TSLP. The antimicrobial activity is primarily mediated by the C-terminal part of the protein. In combination with the previously known cytokine function of TSLP, our result indicates dual functions of the molecule and a previously unknown role in host defense. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Experimental Dermatology
volume
20
issue
12
pages
1004 - 1010
publisher
Wiley-Blackwell
external identifiers
  • wos:000297154000008
  • pmid:22092577
  • scopus:81455139902
ISSN
0906-6705
DOI
10.1111/j.1600-0625.2011.01391.x
language
English
LU publication?
yes
id
5248d733-7e47-4fc9-ba6d-7d2b984dcd70 (old id 2220676)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22092577?dopt=Abstract
date added to LUP
2011-12-02 22:03:44
date last changed
2017-08-27 05:43:05
@article{5248d733-7e47-4fc9-ba6d-7d2b984dcd70,
  abstract     = {Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like cytokine expressed by epithelial cells and reported to be involved in allergic diseases and atopic eczema. The presence of several predicted α-helical regions in TSPL, a structure characterizing many classical antimicrobial peptides (AMPs), prompted us to investigate whether TSLP exerts antimicrobial activities. Recombinant human TSLP exerted antimicrobial activity, particularly against Gram-negative bacteria. Using synthetic overlapping peptide 20-mers of TSLP, it was demonstrated that the antimicrobial effect is primarily mediated by the C-terminal region of the protein. MKK34 (MKKRRKRKVTTNKCLEQVSQLQGLWRRFNRPLLK), a peptide spanning a C-terminal α-helical region in TSLP, showed potent antimicrobial activities, in physiological salt conditions and in the presence of human plasma. Fluorescent studies of peptide-treated bacteria, electron microscopy and liposome leakage models showed that MKK34 exerted membrane-disrupting effects comparable to those of the classical AMP LL-37. Moreover, TSLP was degraded into multiple fragments by staphylococcal V8 proteinase. One major antimicrobial degradation fragment was found to encompass the C-terminal antimicrobial region defined by the MKK34 peptide. We here describe a novel antimicrobial role for TSLP. The antimicrobial activity is primarily mediated by the C-terminal part of the protein. In combination with the previously known cytokine function of TSLP, our result indicates dual functions of the molecule and a previously unknown role in host defense.},
  author       = {Sonesson, Andreas and Kasetty, Gopinath and Olin, Anders and Malmsten, Martin and Mörgelin, Matthias and Sørensen, Ole E and Schmidtchen, Artur},
  issn         = {0906-6705},
  language     = {eng},
  number       = {12},
  pages        = {1004--1010},
  publisher    = {Wiley-Blackwell},
  series       = {Experimental Dermatology},
  title        = {Thymic stromal lymphopoietin exerts antimicrobial activities.},
  url          = {http://dx.doi.org/10.1111/j.1600-0625.2011.01391.x},
  volume       = {20},
  year         = {2011},
}