LL-37-induced human mast cell activation through G protein-coupled receptor MrgX2.

Abstract

Human LL-37 is an important class of cationic antimicrobial peptide (CAP) that is known to stimulate mast cell activation. While many studies have been conducted on LL-37, to date little is known about the functional receptors for LL-37-induced human mast cell activation, in particular in terms of the release of de novo synthesized mediators. Thus, the aim of the present study is to identify the functional receptors for LL-37-induced human mast cell activation in terms of the degranulation and release of de novo synthesized mediators and investigate the downstream signalling pathways involved in mast cell activation. Overall, our study importantly demonstrates that LL-37-induced human mast cell degranulation and release of de novo synthesized mediators function primarily through the activation of MrgX2. We furthermore show that LL-37-induced human mast cell line LAD2 cells are involved in the degranulation and release of IL-8, and that FPRL1 and P2X7 have only a partial effect on IL-8 release, and no effect on mast cell degranulation triggered by LL-37. Instead, we find that silencing the expression of MrgX2 in human mast cell significantly inhibits the LL-37-induced degranulation and release of IL-8. Overall, this effect is associated with the activation of the Gi protein, PLC/PKC/Calcium/NFAT, PI3K/Akt and MAPKs signalling pathways.

• Authors: Yangyang Yu, Yuanyuan Zhang, Yarui Zhang, Yihong Lai, Wenwen Chen, Zhangang Xiao, Wei Zhang, Meiling Jin, Bo Yu
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 49 Pg. 6-12 (Aug 2017) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 28549244 (Publication Type: Journal Article)
• Copyright: Copyright © 2017. Published by Elsevier B.V.

Chemical References

• Antimicrobial Cationic Peptides
• Cathelicidins
• FPR2 protein, human
• Interleukin-8
• MRGPRX2 protein, human
• NFATC Transcription Factors
• Nerve Tissue Proteins
• RNA, Small Interfering
• Receptors, Formyl Peptide
• Receptors, G-Protein-Coupled
• Receptors, Lipoxin
• Receptors, Neuropeptide
• Receptors, Purinergic P2X7
• Extracellular Signal-Regulated MAP Kinases
• Type C Phospholipases

Topics

• Antimicrobial Cationic Peptides
• Calcium Signaling
• Cathelicidins (metabolism)
• Cell Degranulation
• Cells, Cultured
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Humans
• Interleukin-8 (metabolism)
• Mast Cells (physiology)
• NFATC Transcription Factors (metabolism)
• Nerve Tissue Proteins (genetics, metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• RNA, Small Interfering (genetics)
• Receptors, Formyl Peptide (metabolism)
• Receptors, G-Protein-Coupled (genetics, metabolism)
• Receptors, Lipoxin (metabolism)
• Receptors, Neuropeptide (genetics, metabolism)
• Receptors, Purinergic P2X7 (metabolism)
• Type C Phospholipases (metabolism)
• Up-Regulation