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Multiple functions of the new cytokine-based antimicrobial peptide thymic stromal lymphopoietin (TSLP)

Bjerkan, Louise; Sonesson, Andreas LU and Schenck, Karl (2016) In Pharmaceuticals 9(3).
Abstract

Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine, hitherto mostly known to be involved in inflammatory responses and immunoregulation. The human tslp gene gives rise to two transcription and translation variants: a long form (lfTSLP) that is induced by inflammation, and a short, constitutively-expressed form (sfTSLP), that appears to be downregulated by inflammation. The TSLP forms can be produced by a number of cell types, including epithelial and dendritic cells (DCs). lfTSLP can activate mast cells, DCs, and T cells through binding to the lfTSLP receptor (TSLPR) and has a pro-inflammatory function. In contrast, sfTSLP inhibits cytokine secretion of DCs, but the receptor mediating this effect is unknown. Our recent... (More)

Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine, hitherto mostly known to be involved in inflammatory responses and immunoregulation. The human tslp gene gives rise to two transcription and translation variants: a long form (lfTSLP) that is induced by inflammation, and a short, constitutively-expressed form (sfTSLP), that appears to be downregulated by inflammation. The TSLP forms can be produced by a number of cell types, including epithelial and dendritic cells (DCs). lfTSLP can activate mast cells, DCs, and T cells through binding to the lfTSLP receptor (TSLPR) and has a pro-inflammatory function. In contrast, sfTSLP inhibits cytokine secretion of DCs, but the receptor mediating this effect is unknown. Our recent studies have demonstrated that both forms of TSLP display potent antimicrobial activity, exceeding that of many other known antimicrobial peptides (AMPs), with sfTSLP having the strongest effect. The AMP activity is primarily mediated by the C-terminal region of the protein and is localized within a 34-mer peptide (MKK34) that spans the C-terminal α-helical region in TSLP. Fluorescent studies of peptide-treated bacteria, electron microscopy, and liposome leakage models showed that MKK34 exerted membrane-disrupting effects comparable to those of LL-37. Expression of TSLP in skin, oral mucosa, salivary glands, and intestine is part of the defense barrier that aids in the control of both commensal and pathogenic microbes.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
AMP, Immunoregulation, TSLP
in
Pharmaceuticals
volume
9
issue
3
publisher
MDPI AG
external identifiers
  • scopus:84977588416
ISSN
1424-8247
DOI
10.3390/ph9030041
language
English
LU publication?
yes
id
b23dc74d-b01e-415a-9358-97ab4776178d
date added to LUP
2016-11-23 08:54:17
date last changed
2017-09-24 05:03:27
@article{b23dc74d-b01e-415a-9358-97ab4776178d,
  abstract     = {<p>Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine, hitherto mostly known to be involved in inflammatory responses and immunoregulation. The human tslp gene gives rise to two transcription and translation variants: a long form (lfTSLP) that is induced by inflammation, and a short, constitutively-expressed form (sfTSLP), that appears to be downregulated by inflammation. The TSLP forms can be produced by a number of cell types, including epithelial and dendritic cells (DCs). lfTSLP can activate mast cells, DCs, and T cells through binding to the lfTSLP receptor (TSLPR) and has a pro-inflammatory function. In contrast, sfTSLP inhibits cytokine secretion of DCs, but the receptor mediating this effect is unknown. Our recent studies have demonstrated that both forms of TSLP display potent antimicrobial activity, exceeding that of many other known antimicrobial peptides (AMPs), with sfTSLP having the strongest effect. The AMP activity is primarily mediated by the C-terminal region of the protein and is localized within a 34-mer peptide (MKK34) that spans the C-terminal α-helical region in TSLP. Fluorescent studies of peptide-treated bacteria, electron microscopy, and liposome leakage models showed that MKK34 exerted membrane-disrupting effects comparable to those of LL-37. Expression of TSLP in skin, oral mucosa, salivary glands, and intestine is part of the defense barrier that aids in the control of both commensal and pathogenic microbes.</p>},
  articleno    = {41},
  author       = {Bjerkan, Louise and Sonesson, Andreas and Schenck, Karl},
  issn         = {1424-8247},
  keyword      = {AMP,Immunoregulation,TSLP},
  language     = {eng},
  month        = {09},
  number       = {3},
  publisher    = {MDPI AG},
  series       = {Pharmaceuticals},
  title        = {Multiple functions of the new cytokine-based antimicrobial peptide thymic stromal lymphopoietin (TSLP)},
  url          = {http://dx.doi.org/10.3390/ph9030041},
  volume       = {9},
  year         = {2016},
}