LL-37 (trifluoroacetate salt)
(Synonyms: 人源杀菌肽LL37) 目录号 : GC14377
An antimicrobial peptide
Cas No.:154947-66-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
HaCaT cells |
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Preparation Method |
HaCaT cells were transfected with a 2 μg of empty vector and 0.1, 0.5, 1, or 2 μg of LL-37 plasmids for 6 h and then internalized with P. gingivalis (MOI 100, 6 h) using the antibiotic protection assay. Total RNA was extracted after 18 h. |
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Reaction Conditions |
0.1, 0.5, 1, or 2 μg; 6 h |
|
Applications |
The qRT-PCR results showed that compared with the control cells, the number of live P. gingivalis was significantly reduced by 0.79, 0.62, and 0.69 times in cells transfected with 0.5, 1, or 2 μg of LL 37 plasmids, respectively. LL 37 mRNA expression gradually increased significantly as transfected with 0.1, 0.5, or 1 μg of LL 37 plasmids, which was followed by a decrease and reached a peak in cells treated with 1 μg of LL 37 plasmids. |
| Animal experiment [2]: | |
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Animal models |
BALB/c female mice |
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Preparation Method |
Mice were intravenously injected with PBS (200 μl) or LL 37 (3 μg/200 μl in PBS) just prior to CLP or sham operation. Peritoneal exudates (3 ml) and blood were collected 14–16 h after the operation, and the number of bacteria and inflammatory cells was determined. |
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Dosage form |
3 μg/200 μl in PBS; i.v. |
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Applications |
LL 37 administration significantly reduced the bacterial load in the peritoneal exudates (PBS-CLP vs LL-37-CLP) as well as blood. |
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References: [1]. Yang X, et al. LL-37-Induced Autophagy Contributed to the Elimination of Live Porphyromonas gingivalis Internalized in Keratinocytes. Front Cell Infect Microbiol. 2020 Oct 15;10:561761. [2]. Kumagai Y, et al. Antimicrobial peptide LL-37 ameliorates a murine sepsis model via the induction of microvesicle release from neutrophils. Innate Immun. 2020 Oct;26(7):565-579. |
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LL-37 contains 37 amino acid residues with the first two leucine residues (L1LGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES37) and mostly exists in epithelial cells and neutrophils.
In vitro experiment it shown that treatment with 4 and 10 μM LL-37 reduced both the number and viability of human osteoblast-like MG63 cell.[2] In vitro, the pretreatment of pMSCs with 1 and 10 μg/mL of LL-37 had not effect on the migratory cells ability. But the pretreatment with 1 μg/mL of LL-37 increased the migratory potential of pMSCs after 48 h.[4] In vitro study it indicated that at 1 μmol/L concentrations of LL-37 for 24 hours, LL-37 prevented LPS-induced stimulation of MCP-1 expression analyzed both on transcript and on protein levels, but had no effect on toll-like receptor (TLR)2 and TLR4 transcript expression. In the meanwhile, treatment with 0.1 and 1 μmol/L LL-37 for 60 minutes in PDL cell induced immunoreactivity for LL-37.[5]
In vivo study it suggested that treatment with 2 μg/mouse of LL-37 intravenously improves the survival of CLP septic mice in a dose-dependent effect. LL-37 ameliorates the level of ectosomes with higher antibacterial potential, result in reducing the bacterial load in CLP mice.[1] LL-37 dose-dependently (1, 3, or 10 μg/ml) induced ectosome release from neutrophil. Injection LL-37 supressed the infiltration of polymorphonuclear cells in CLP mice, where the bacterial burden and inflammatory response are decreased.[3]
References:
[1].Nagaoka I, et al. Therapeutic Potential of Cathelicidin Peptide LL-37, an Antimicrobial Agent, in a Murine Sepsis Model. Int J Mol Sci. 2020 Aug 19;21(17):5973.
[2].Bankell E, et al. LL-37-induced caspase-independent apoptosis is associated with plasma membrane permeabilization in human osteoblast-like cells. Peptides. 2021 Jan;135:170432.
[3].Kumagai Y, et al. Antimicrobial peptide LL-37 ameliorates a murine sepsis model via the induction of microvesicle release from neutrophils. Innate Immun. 2020 Oct;26(7):565-579.
[4].Oliveira-Bravo M, et al. LL-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells. Stem Cell Res Ther. 2016 Dec 30;7(1):189.
[5].Aidoukovitch A, et al. The host defense peptide LL-37 is internalized by human periodontal ligament cells and prevents LPS-induced MCP-1 production. J Periodontal Res. 2019 Dec;54(6):662-670.
LL-37含有37个氨基酸残基，前两个亮氨酸残基（L1LGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES37），主要存在于上皮细胞和中性粒细胞中。
体外实验表明，用 4 μM 和 10 μM LL-37 处理会降低人成骨细胞样 MG63 细胞的数量和活力。[2] 在体外，用1和10μg/mL的LL-37对迁移细胞能力没有影响。但用1 μg/mL LL-37预处理48 h后pMSCs的迁移潜能增加。[4] 体外研究表明，在1 μmol/L浓度的LL-37下处理24小时，LL-37 阻止了 LPS 诱导的 MCP-1 表达刺激，在转录本和蛋白质水平上进行了分析，但对 Toll 样受体 (TLR)2 和 TLR4 转录本表达没有影响。同时，0.1 和 1 μmol/L LL-37 在 PDL 细胞中处理 60 分钟可诱导 LL-37 的免疫反应。[5]
体内研究表明，每只小鼠静脉注射 2 μg LL-37 可提高 CLP 脓毒症小鼠的存活率，并具有剂量依赖性效应。 LL-37 改善具有更高抗菌潜力的胞外体水平，从而减少 CLP 小鼠的细菌负荷。[1] LL-37 剂量依赖性（1、3 或 10 μg/ml）诱导中性粒细胞胞外体释放。注射 LL-37 抑制了 CLP 小鼠体内多形核细胞的浸润，从而降低了细菌负荷和炎症反应。[3]
| Cas No. | 154947-66-7 | SDF | |
| 别名 | 人源杀菌肽LL37 | ||
| Canonical SMILES | CC[C@]([C@@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/C/N=C(O)/[C@](/N=C(O)/[C@](N)([H])CC(C)C)([H])CC(C)C)([H])CC(O)=O)([H])CC1=CC=CC=C1)([H])CC2=CC=CC=C2)([H])CCCNC(N)=N | ||
| 分子式 | C205H340N60O53 | 分子量 | 4493.32 |
| 溶解度 | Water: 1 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.2226 mL | 1.1128 mL | 2.2255 mL |
| 5 mM | 0.0445 mL | 0.2226 mL | 0.4451 mL |
| 10 mM | 0.0223 mL | 0.1113 mL | 0.2226 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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工作液浓度： mg/ml；
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2.
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Therapeutic Potential of Cathelicidin Peptide LL-37, an Antimicrobial Agent, in a Murine Sepsis Model
Int J Mol Sci2020 Aug 19;21(17):5973.PMID: 32825174DOI: 10.3390/ijms21175973
Among the mechanisms put-up by the host to defend against invading microorganisms, antimicrobial peptides represent the first line. In different species of mammals, the cathelicidin family of antimicrobial peptides AMPs has been identified, and in humans, LL-37 is the only type of cathelicidin identified. LL-37 has many different biological activities, such as regulation of responses to inflammation, besides its lipopolysaccharide (LPS)-neutralizing and antimicrobial and activities. Recently, employing a murine septic model that involves cecal ligation and puncture (CLP), we examined the effect of LL-37. The results indicated that LL-37 exhibits multiple protective actions on septic mice; firstly, the survival of CLP mice was found to be improved by LL-37 by the suppression of the macrophage pyroptosis that induces the release of pro-inflammatory cytokines (such as IL-1β) and augments inflammatory reactions in sepsis; secondly, the release of neutrophil extracellular traps (NETs), which have potent bactericidal activity, is enhanced by LL-37, and protects mice from CLP-induced sepsis; thirdly, LL-37 stimulates neutrophils to release antimicrobial microvesicles (ectosomes), which improve the pathological condition of sepsis. These findings indicate that LL-37 protects CLP septic mice through at least three mechanisms, i.e., the suppression of pro-inflammatory macrophage pyroptosis and the release of antimicrobial NETs (induction of NETosis) and ectosomes from neutrophils. Thus, LL-37 can be a potential therapeutic candidate for sepsis due to its multiple properties, including the modulation of cell death (pyroptosis and NETosis) and the release of antimicrobial NETs and ectosomes as well as its own bactericidal and LPS-neutralizing activities.
Roles and Mechanisms of Human Cathelicidin LL-37 in Cancer
Cell Physiol Biochem2018;47(3):1060-1073.PMID: 29843147DOI: 10.1159/000490183
LL-37, the C-terminal peptide of human cathelicidin antimicrobial peptide (CAMP, hCAP18), reportedly increases resistance to microbial invasion and exerts important physiological functions in chemotaxis, promotion of wound closure, and angiogenesis. Accumulating evidence indicates that LL-37 also plays a significant role in human cancer. LL-37 induces tumorigenic effects in cancers of the ovary, lung, breast, prostate, pancreas, as well as in malignant melanoma and skin squamous cell carcinoma. In contrast, LL-37 displays an anti-cancer effect in colon cancer, gastric cancer, hematologic malignancy and oral squamous cell carcinoma. Mechanistically, LL-37-induced activation of membrane receptors and subsequent signaling pathways lead to alteration of cellular functions. Different membrane receptors on various cancer cells appear to be responsible for the tissue-specific effects of LL-37. Meanwhile, the findings that vitamin D-dependent induction of cathelicidin in human macrophages activates the anti-cancer activity of tumor-associated macrophages (TAMs) and enhances antibody-dependent cellular cytotoxicity (ADCC) support critical roles of vitamin D-dependent induction of cathelicidin in cancer progression. This review describes novel advances involving the roles and mechanisms of human cathelicidin LL-37 in cancer.
Antimicrobial Peptide LL-37 Drives Rosacea-Like Skin Inflammation in an NLRP3-Dependent Manner
J Invest Dermatol2021 Dec;141(12):2885-2894.e5.PMID: 33745908DOI: 10.1016/j.jid.2021.02.745
Rosacea is a chronic inflammatory skin disease characterized by immune response-dependent erythema and pustules. Although the precise etiology of rosacea remains elusive, its pathogenesis is reportedly associated with an increased level of antimicrobial peptide LL-37. However, molecular mechanisms underlying the progression of rosacea via LL-37 remain poorly understood. Here, we examined the potential role of LL-37 in rosacea-like skin inflammatory phenotypes at a molecular level. Our in vitro data demonstrated that LL-37 promotes NLRP3-mediated inflammasome activation in lipopolysaccharide-primed macrophages, indicated by the processing of caspase-1 and IL-1β. LL-37 was internalized into the cytoplasm of macrophages through P2X7 receptor-mediated endocytosis. Intracellular LL-37 triggered the assembly and activation of NLRP3-ASC inflammasome complex by facilitating lysosomal destabilization. Consistent with these in vitro results, intradermal LL-37 administration induced in vivo caspase-1 activation and ASC speck formation in the skin of Nlrp3-expressing, but not in Nlrp3-deficient, mice. Intradermal injection of LL-37 elicited profound recruitment of inflammatory Gr1+ cells and subsequent skin inflammation. However, LL-37-induced rosacea-like skin inflammation was significantly abrogated in Nlrp3-deficient mice. Furthermore, an NLRP3-specific inhibitor, MCC950, markedly reduced LL-37-triggered rosacea-like phenotypes. Taken together, our findings clearly indicate that NLRP3 inflammasome activation plays a crucial role in LL-37-induced skin inflammation and rosacea pathogenesis.
The Potential of Human Peptide LL-37 as an Antimicrobial and Anti-Biofilm Agent
Antibiotics (Basel)2021 May 29;10(6):650.PMID: 34072318DOI: 10.3390/antibiotics10060650
The rise in antimicrobial resistant bacteria threatens the current methods utilized to treat bacterial infections. The development of novel therapeutic agents is crucial in avoiding a post-antibiotic era and the associated deaths from antibiotic resistant pathogens. The human antimicrobial peptide LL-37 has been considered as a potential alternative to conventional antibiotics as it displays broad spectrum antibacterial and anti-biofilm activities as well as immunomodulatory functions. While LL-37 has shown promising results, it has yet to receive regulatory approval as a peptide antibiotic. Despite the strong antimicrobial properties, LL-37 has several limitations including high cost, lower activity in physiological environments, susceptibility to proteolytic degradation, and high toxicity to human cells. This review will discuss the challenges associated with making LL-37 into a viable antibiotic treatment option, with a focus on antimicrobial resistance and cross-resistance as well as adaptive responses to sub-inhibitory concentrations of the peptide. The possible methods to overcome these challenges, including immobilization techniques, LL-37 delivery systems, the development of LL-37 derivatives, and synergistic combinations will also be considered. Herein, we describe how combination therapy and structural modifications to the sequence, helicity, hydrophobicity, charge, and configuration of LL-37 could optimize the antimicrobial and anti-biofilm activities of LL-37 for future clinical use.
Design of Antimicrobial Peptides: Progress Made with Human Cathelicidin LL-37
Adv Exp Med Biol2019;1117:215-240.PMID: 30980360DOI: 10.1007/978-981-13-3588-4_12
The incorporation of the innate immune system into humans is essential for survival and health due to the rapid replication of invading microbes and the delayed action of the adaptive immune system. Antimicrobial peptides are important components of human innate immunity. Over 100 such peptides have been identified in various human tissues. Human cathelicidin LL-37 is best studied, and there has been a growing interest in designing new peptides based on LL-37. This chapter describes the alternative processing of the human cathelicidin precursor, protease digestion, and lab cutting of LL-37. Both a synthetic peptide library and structure-based design are utilized to identify the active regions. Although challenging, the determination of the 3D structure of LL-37 enabled the identification of the core antimicrobial region. The minimal region of LL-37 can be function-dependent. We discuss the design and potential applications of LL-37 into antibacterial, antibiofilm, antiviral, antifungal, immune modulating, and anticancer peptides. LL-37 has been engineered into 17BIPHE2, a stable, selective, and potent antimicrobial, antibiofilm, and anticancer peptide. Both 17BIPHE2 and SAAP-148 can eliminate the ESKAPE pathogens and show topical in vivo antibiofilm efficacy. Also discussed are other application strategies, including peptide formulation, antimicrobial implants, and peptide-inducing factors such as vitamin D and sunlight. Finally, we summarize what we learned from peptide design based on human LL-37.