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Thymic stromal lymphopoietin exerts antimicrobial activities
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
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2011 (English)In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 20, no 12, 1004-1010 p.Article in journal (Refereed) Published
Abstract [en]

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 a-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 a-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.

Place, publisher, year, edition, pages
2011. Vol. 20, no 12, 1004-1010 p.
Keyword [en]
antimicrobial peptides, atopic eczema, bacteria, fungi, innate immunity
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-165682DOI: 10.1111/j.1600-0625.2011.01391.xISI: 000297154000008OAI: oai:DiVA.org:uu-165682DiVA: diva2:474897
Available from: 2012-01-10 Created: 2012-01-09 Last updated: 2012-01-10Bibliographically approved

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