• MeSH
• bakteriální proteiny metabolismus   MeSH
• imunoglobuliny metabolismus   MeSH
• lidé MeSH
• metaloproteasy metabolismus   MeSH
• Staphylococcus aureus enzymologie   MeSH
• substrátová specifita MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakty MeSH

• MeSH
• ELISA MeSH
• epitopy MeSH
• imunoglobulin A sekreční chemie   metabolismus   MeSH
• imunoglobulin G chemie   metabolismus   MeSH
• imunoglobulin M chemie   metabolismus   MeSH
• lidé MeSH
• Staphylococcus aureus enzymologie   MeSH
• Check Tag
• lidé MeSH

• MeSH
• aktivace lymfocytů účinky léků   MeSH
• imunoglobuliny analýza   biosyntéza   MeSH
• lidé MeSH
• lymfocyty imunologie   účinky záření   MeSH
• metaloproteasy farmakologie   MeSH
• Staphylococcus aureus enzymologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH

LL-37, the only human cathelicidin that is released during inflammation, is a potent regulator of immune responses by facilitating delivery of oligonucleotides to intracellular TLR-9, thereby enhancing the response of human plasmacytoid dendritic cells (pDCs) to extracellular DNA. Although important for pathogen recognition, this mechanism may facilitate development of autoimmune diseases. In this article, we show that citrullination of LL-37 by peptidyl-arginine deiminases (PADs) hindered peptide-dependent DNA uptake and sensing by pDCs. In contrast, carbamylation of the peptide (homocitrullination of Lys residues) had no effect. The efficiency of LL-37 binding to oligonucleotides and activation of pDCs was found to be inversely proportional to the number of citrullinated residues in the peptide. Similarly, preincubation of carbamylated LL-37 with PAD2 abrogated the peptide's ability to bind DNA. Conversely, LL-37 with Arg residues substituted by homoarginine, which cannot be deiminated, elicited full activity of native LL-37 regardless of PAD2 treatment. Taken together, the data showed that citrullination abolished LL-37 ability to bind DNA and altered the immunomodulatory function of the peptide. Both activities were dependent on the proper distribution of guanidinium side chains in the native peptide sequence. Moreover, our data suggest that cathelicidin/LL-37 is citrullinated by PADs during NET formation, thus affecting the inflammatory potential of NETs. Together this may represent a novel mechanism for preventing the breakdown of immunotolerance, which is dependent on the response of APCs to self-molecules (including cell-free DNA); overactivation may facilitate development of autoimmunity.

• MeSH
• autoimunita imunologie   MeSH
• biologický transport MeSH
• buněčné linie MeSH
• citrulin metabolismus   MeSH
• citrulinace fyziologie   MeSH
• dendritické buňky imunologie   MeSH
• DNA imunologie   metabolismus   MeSH
• imunologická tolerance imunologie   MeSH
• kationické antimikrobiální peptidy metabolismus   MeSH
• lidé MeSH
• myši MeSH
• peptidylarginindeiminasy metabolismus   MeSH
• RAW 264.7 buňky MeSH
• volné cirkulující nukleové kyseliny imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH