The role of the Src family kinase Lyn in the immunomodulatory activities of cathelicidin peptide LL-37 on monocytic cells

Journal of Leukocyte Biology

Alexander Ramin¹  Robert E. W. Hancock¹  Kenneth W. Harder¹  Niall C. J. Filewod¹  Patricia Cho¹  Anastasia Nijnik¹  Jelena Pistolic¹  Reza Falsafi¹ 

[1] Department of Microbiology and Immunology, University of British Columbia, Vancouver, CanadaDepartment of Microbiology and Immunology, University of British Columbia, Vancouver, CanadaDepartment of Microbiology and Immunology, University of British Columbia, Vancouver, Canada

关键词: monocyte;    chemokine;    signaling pathways;   

DOI  :  10.1189/jlb.0411191

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Cathelicidin LL-37 is a multifunctional, immunomodulatory and antimicrobial host-defense peptide of the human immune system. Here, we identified the role of SFKs in mediating the chemokine induction activity of LL-37 in monocytic cells. LL-37 induced SFK phosphorylation; and chemical inhibitors of SFKs suppressed chemokine production in response to LL-37 stimulation. SFKs were required for the downstream activation of AKT, but Ca2+-flux and MAPK induction were SFK-independent. Through systematic siRNA knockdown of SFK members, a requirement for Lyn in mediating LL-37 activity was identified. The involvement of Lyn in cathelicidin activities was further confirmed using Lyn-knockout mouse BMDMs. The role of SFKs and Lyn was also demonstrated in the activities of the synthetic cationic IDR peptides, developed as novel, immunomodulatory therapeutics. These findings elucidate the common molecular mechanisms mediating the chemokine induction activity of natural and synthetic cationic peptides in monocytic cells and identify SFKs as a potential target for modulating peptide responses.

【 授权许可】

Unknown