title: Thymic stromal lymphopoietin exerts antimicrobial activities.
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.
authors.affiliation: Divisions of Dermatology and Venereology Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden. andreas.sonesson@med.lu.se
authors.forename: Andreas
authors.initials: A
authors.lastname: Sonesson
authors.forename: Gopinath
authors.initials: G
authors.lastname: Kasetty
authors.forename: Anders I
authors.initials: AI
authors.lastname: Olin
authors.forename: Martin
authors.initials: M
authors.lastname: Malmsten
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.forename: Ole E
authors.initials: OE
authors.lastname: Sørensen
authors.forename: Artur
authors.initials: A
authors.lastname: Schmidtchen
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000378:metabolism / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism; D002176:Candida albicans / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology; D011994:Recombinant Proteins / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000201:enzymology; D013212:Staphylococcus epidermidis / Q000187:drug effects; D054804:Cathelicidins; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D016207:Cytokines; D008081:Liposomes; D010446:Peptide Fragments; D011994:Recombinant Proteins; D010447:Peptide Hydrolases; D019272:Leukocyte Elastase; D008666:Metalloendopeptidases; C043859:pseudolysin, Pseudomonas aeruginosa; D054804:Cathelicidins; D000094632:Thymic Stromal Lymphopoietin