title: The modulatory effect of TLR2 on LL-37-induced human mast cells activation.
abstract: The sole and endogenous anti-microbial peptide LL-37 is a significant effector molecule in the innate host defense system. Apart from its broadly direct anti-microbial activity, the peptide also activates mast cell in respect of allergic diseases and inflammation. On the other hand, mast cell can be activated by Toll-like receptors (TLRs) which are at the center of innate immunity. It was the aim of the study to illustrate the modulatory effect of TLR2 ligands peptidoglycan (PGN) and tripalmitoyl-S-glycero-Cys-(Lys)4 (Pam3CSK4) on LL-37 induced LAD2 cells (a human mast cell line) activation. LL-37 induced LAD2 cells degranulation and the release of IL-8. TLR2 ligands didn't induce LAD2 cells degranulation, but triggered the release of IL-8. Incubation with PGN or Pam3CSK4 significantly suppressed LL-37-induced degranulation through inhibition of calcium mobilization from LAD2 cells. Similarly, the release of IL-8 was inhibited when LAD2 cells were co-stimulated with TLR2 ligands and LL-37. Studies with inhibitors of key enzymes involved in mast cell signaling indicated that the release of IL-8 induced by TLR2 ligands and LL-37 involved the activation of the PI3K, ERK, JNK and calcineurin signaling pathways. In contrast, p38 activation down-regulated the release of IL-8 induced by TLR2 ligands and LL-37. Taken together, these observations suggest that activation of human mast cells by LL-37 could be modified by TLR2 ligands and the function of human mast cells could be switched from allergic reactions to innate immune response.
authors.affiliation: Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 518036, PR China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: School of Medicine, Shenzhen University, Shenzhen, Guangdong, PR China.
authors.forename: Yang-Yang
authors.initials: YY
authors.lastname: Yu
authors.affiliation: Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 518036, PR China.
authors.forename: Ya-Rui
authors.initials: YR
authors.lastname: Zhang
authors.affiliation: Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 518036, PR China. Electronic address: zhangweispace@yeah.net.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 518036, PR China; Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China. Electronic address: yubomd@hotmail.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000276:immunology*; D002460:Cell Line; D003594:Cytoplasmic Granules / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007155:Immunologic Factors / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology*; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D007155:Immunologic Factors; D016209:Interleukin-8; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D054804:Cathelicidins
keywords: Human mast cells; LL-37; Toll-like receptor 2 (TLR2)