LL-37 and Fragments

Introduction

LL-37 is a neutrophil granule/epithelial cell-derived antimicrobial peptide(amino acid sequence: LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES), and is the only member of the human cathelicidin family. About 30 cathelicidin members have been described in mammals, but so far only hCAP-18 has been identified in humans. hCAP-18 originates LL-37 through the cleavage between Ala103 and Leu104. LL-37 is produced by several cell types and tissues, including neutrophils, NK cells, macrophages, monocytes, and keratinocytes. LL-37 is involved in lung infection and inflammation, and its expression can be localized at inflammation sites. The local overexpression of LL-37 has been identified in the lesional skin of palmoplantar pustulosis. The local overexpression of LL-37 has been identified in the lesional skin of palmoplantar pustulosis. The protective effect of LL-37 against sepsis-induced death has been reported in rats.

Mechanism of action

LL-37 induces cell migration via transactivation of EGFR and promotes cell proliferation via G-protein coupled with formyl-peptide receptor 2 (FRP2). Furthermore, LL-37 promotes P2 × 7 activation, which leads to intracellular clearance of bacteria and induces proliferation and migration by ERBb2 signaling. Also, this peptide induces angiogenesis, wound healing and apoptosis of some cell types, apart from prompting both pro- and anti-inflammatory functions, depending on the microenvironment and disease background. LL-37 is effective in killing bacteria by destroying cell membranes. LL-37 exerts different effects on T-cell response and production of inflammatory factors by PBMCs, which varied according to the T-cell activation state at the time of LL-37 treatment.

Application of LL-37 and Fragments

An analog of the LL-37 peptide, sLL-37, is a catholicizing-related or modified antimicrobial peptide that exhibits an antiproliferative effect against cancer cells. In the current study, it was suggested that the administration of LL-37 and its analog sLL-37 could significantly prevent the procession of acute lung injury and the accumulation of migrated neutrophils by inactivating migration-related pathways (FAK and MAPKs), demonstrating the therapeutic potential for sepsis-induced acute lung injury.

References

1. Meltem Karsiyaka Hendek., Merve Erkmen Almaz., Ebru Olgun., &Ucler Kisa. (2018). Salivary LL-37 and Periodontal Health in Children Exposed to Passive Smoking. Int J Paediatr Dent.
2. Xiuchuan Qin., Guangfa Zhu., Lixue Huang., Wenwei Zhang., Yan Huang., &Xin Xi. (2018). LL-37 and its analog FF/CAP18 attenuate neutrophil migration in sepsis-induced acute lung injury. J Cell Biochem, 1-9.
3. Dominique Sternadt Alexandre-Ramosa.,Amandda Évelin Silva-Carvalhoa., Mariella Guimarães Lacerda., Teresa Raquel Tavares Serejo., Octávio Luiz Franco., Rinaldo Wellerson Pereira., Juliana Lott Carvalho.,Francisco Assis Roch Neves., &Felipe Saldanha-Araujo. (2018). LL-37 treatment on human peripheral blood mononuclear cells modulates immune response and promotes regulatory T-cells generation. Biomed Pharmacother, 108, 1584-1590.