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Citrullination Alte...
Citrullination Alters the Antibacterial and Anti-Inflammatory Functions of the Host Defense Peptide Canine Cathelicidin K9CATH In Vitro
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Al Adwani, Salma (author)
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- Padhi, Avinash (author)
- Karolinska Institutet
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Karadottir, Harpa (author)
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- Mörman, Cecilia (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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- Gräslund, Astrid (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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- Végvári, Ákos (author)
- Karolinska Institutet
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- Johansson, Jan (author)
- Karolinska Institutet
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- Rising, Anna (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Karolinska Institutet,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB),Karolinska Institute
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- Agerberth, Birgitta (author)
- Karolinska Institutet
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- Bergman, Peter (author)
- Karolinska Institutet
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(creator_code:org_t)
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- 2021-08-01
- 2021
- English.
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In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 207:3, s. 974-984
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.4...
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Abstract
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- K9CATH is the sole cathelicidin in canines (dogs) and exhibits broad antimicrobial activity against both Gram-positive and Gram-negative bacteria. K9CATH also modulates inflammatory responses and binds to LPS. These activities depend on the secondary structure and a net-positive charge of the peptide. Peptidylarginine deiminases (PAD) convert cationic peptidyl arginine to neutral citrulline. Thus, we hypothesized that citrullination is a biologically relevant modification of the peptide that would reduce the antibacterial and LPS-binding activities of K9CATH. Recombinant PAD2 and PAD4 citrullinated K9CATH to various extents and circular dichroism spectroscopy revealed that both native and citrullinated K9CATH exhibited similar α-helical secondary structures. Notably, citrullination of K9CATH reduced its bactericidal activity, abolished its ability to permeabilize the membrane of Gram-negative bacteria and reduced the hemolytic capacity. Electron microscopy showed that citrullinated K9CATH did not cause any morphological changes of Gram-negative bacteria, whereas the native peptide caused clear alterations of membrane integrity, concordant with a rapid bactericidal effect. Finally, citrullination of K9CATH impaired its capacity to inhibit LPS-mediated release of proinflammatory molecules from mouse and canine macrophages. In conclusion, citrullination attenuates the antibacterial and the LPS-binding properties of K9CATH, demonstrating the importance of a net positive charge for antibacterial lysis of bacteria and LPS-binding effects and suggests that citrullination is a means to regulate cathelicidin activities.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- LANTBRUKSVETENSKAPER -- Veterinärmedicin -- Patobiologi (hsv//swe)
- AGRICULTURAL SCIENCES -- Veterinary Science -- Pathobiology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Al Adwani, Salma
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Padhi, Avinash
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Karadottir, Harp ...
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Mörman, Cecilia
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Gräslund, Astrid
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Végvári, Ákos
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show more...
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Johansson, Jan
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Rising, Anna
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Agerberth, Birgi ...
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Bergman, Peter
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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- AGRICULTURAL SCIENCES
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AGRICULTURAL SCI ...
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and Veterinary Scien ...
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and Pathobiology
- Articles in the publication
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Journal of Immun ...
- By the university
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Stockholm University
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Karolinska Institutet
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Swedish University of Agricultural Sciences