• Title/Summary/Keyword: LL37

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Application of Antimicrobial Peptide LL-37 as an Adjuvant for Middle East Respiratory Syndrome-Coronavirus Antigen Induces an Efficient Protective Immune Response Against Viral Infection After Intranasal Immunization

  • Ju Kim;Ye Lin Yang;Yongsu Jeong;Yong-Suk Jang
    • IMMUNE NETWORK
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    • v.22 no.5
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    • pp.41.1-41.16
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    • 2022
  • The human antimicrobial peptide LL-37 has chemotactic and modulatory activities in various immune cells, including dendritic cells. Because of its characteristics, LL-37 can be considered an adjuvant for vaccine development. In this study, we confirmed the possible adjuvant activity of LL-37 in mucosal vaccine development against Middle East respiratory syndrome-coronavirus (MERS-CoV) by means of intranasal immunization in C57BL/6 and human dipeptidyl peptidase 4 (hDPP4)-transgenic (hDPP4-Tg) mice. Intranasal immunization using the receptor-binding domain (RBD) of MERS-CoV spike protein (S-RBD) recombined with LL-37 (S-RBD-LL-37) induced an efficient mucosal IgA and systemic IgG response with virus-neutralizing activity, compared with S-RBD. Ag-specific CTL stimulation was also efficiently induced in the lungs of mice that had been intranasally immunized with S-RBD-LL-37, compared with S-RBD. Importantly, intranasal immunization of hDPP4-Tg mice with S-RBD-LL-37 led to reduced immune cell infiltration into the lungs after infection with MERS-CoV. Finally, intranasal immunization of hDPP4-Tg mice with S-RBD-LL-37 led to enhanced protective efficacy, with increased survival and reduced body weight loss after challenge infection with MERS-CoV. Collectively, these results suggest that S-RBD-LL-37 is an effective intranasal vaccine candidate molecule against MERS-CoV infection.

Prokaryotic Selectivity, Anti-endotoxic Activity and Protease Stability of Diastereomeric and Enantiomeric Analogs of Human Antimicrobial Peptide LL-37

  • Nan, Yong-Hai;Lee, Bong-Ju;Shin, Song-Yub
    • Bulletin of the Korean Chemical Society
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    • v.33 no.9
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    • pp.2883-2889
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    • 2012
  • LL-37 is the only antimicrobial peptide (AMP) of the human cathelicidin family. In addition to potent antimicrobial activity, LL-37 is known to have the potential to inhibit lipolysaccharide (LPS)-induced endotoxic effects. To provide the stability to proteolytic digestion and increase prokaryotic selectivity and/or anti-endotoxic activity of two Lys/Trp-substituted 19-meric antimicrobial peptides (a4-W1 and a4-W2) designed from IG-19 (residues 13-31 of LL-37), we synthesized the diastereomeric peptides (a4-W1-D and a4-W2-D) with D-amino acid substitution at positions 3, 7, 10, 13 and 17 of a4-W1 and a4-W2, respectively and the enantiomeric peptides (a4-W1-E and a4-W2-E) composed D-amino acids. The diastereomeric peptides exhibited the best prokaryotic selectivity and effective protease stability, but no or less anti-endotoxic activity. In contrast, the enantiomeric peptides had not only prokaryotic selectivity and anti-endotoxic activity but also protease stability. Our results suggest that the hydrophobicity and ${\alpha}$-helicity of the peptide is important for anti-endotoxic activity. In particular, the enantiomeric peptides showed potent anti-endotoxic and LPS-neutralizing activities comparable to that of LL-37. Taken together, both a4-W1-E and a4-W2-E holds promise as a template for the development of peptide antibiotics for the treatment of endotoxic shock and sepsis.

Expression of Recombinant Hybrid Peptide Gaegurin4 and LL37 using Fusion Protein in E. coli (Glutathione S-Transferase에 융합한 재조합 Hybrid Peptide Gaegurin-LL37의 대장균에서의 발현)

  • Bayarbat, Ishvaanjil;Lee, Jae-Hag;Lee, Soon-Youl
    • Microbiology and Biotechnology Letters
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    • v.40 no.2
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    • pp.92-97
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    • 2012
  • Antimicrobial peptides (AMPs) are important components of living organisms acting against Gram-negative and Gram-positive bacterial and fungal pathogens. Cathelicidin human peptides have a variety of biological activities that can be used in clinical applications. AMPs are not produced naturally in large quantities, and chemical synthesis is also economically impractical, especially for long peptides. Therefore, as an alternative, heterologous expression of AMPs by recombinant techniques has been studied as a means to reduce production costs. E. coli is an excellent host for the expression of AMPs, as well as other recombinant proteins, because of the low cost involved and its easy manipulation. However, overexpression of AMPs in E. coli has been shown to cause difficulties resulting from the toxicity of the subsequently produced AMPs. Therefore, fusion expression was theorized to be a solution to this problem. In this study, AMPs were expressed as fused proteins with the glutathione S-transferase (GST) binding protein to protect against the toxicity of AMPs when expressed in E. coli. The LL37, and hybrid gaegurin and LL37 (GGN4(1-16)-LL37(17-32), which we designated as GL32, peptides were expressed as GST-fusion proteins in E. coli and the fusion proteins were then purified by affinity columns. The purified peptides were obtained by removal of GST and were confirmed by western blot analysis. The purified antimicrobial peptides then demonstrated antimicrobial activities against Gram-negative and Gram-positive bacterial strains.

An Improved Incremental LL(1) Parsing Method (개선된 점진적 LL(1) 파싱 방법)

  • Lee, Gyung-Ok
    • Journal of KIISE:Software and Applications
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    • v.37 no.6
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    • pp.486-490
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    • 2010
  • Incremental parsing has been researched in the intention that the parse result of the original string is reused in the parsing of a new string. This paper proposes an improved method of the previous incremental LL(1) parser with nonterminal lookahead symbols. The previous work is time-inefficient because it repeatedly performs unnecessary steps when an error occurs. This paper gives a solution for the problem.

Testing of Extended PLR Grammars (확장된 PLR 문법의 테스팅)

  • Lee, Gyung-Ok
    • Journal of KIISE:Software and Applications
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    • v.37 no.1
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    • pp.51-53
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    • 2010
  • Extended PLR grammars are a large subclass of LR grammars and have good property of LL grammars. On the other hand, a testing algorithm of extended PLR grammars has not been given. The paper presents an algorithm for the testing of extended PLR grammars.

Computation of Reusable Points in Incremental LL(1) Parsing (점진적 LL(1) 구문분석에서의 재사용 시점의 계산)

  • Lee, Gyung-Ok
    • Journal of KIISE:Software and Applications
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    • v.37 no.11
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    • pp.845-850
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    • 2010
  • Incremental parsing has been developed to reuse the parse result of the original string during the parsing of a new string. The previous incremental LL(1) parsing methods precomputed the reusable point information before parsing and used it during parsing. This paper proposes an efficient reusable point computation by factoring the common part of the computation. The common symbol storing method and the distance storing method were previously suggested to find the reusable point, and by combining the methods, this paper gives the storing method of the distance to common symbols. Based on it, an efficient incremental LL(1) parser is constructed.

Simplification of Covering Transformation into LL Grammars (LL 문법으로의 커버링 변환의 단순화)

  • Lee, Gyung-Ok
    • Journal of KIISE:Computer Systems and Theory
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    • v.37 no.6
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    • pp.319-322
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    • 2010
  • Extended PLR grammars are currently the largest subclass of LR grammars whose grammars are transformed into LL grammars satisfying covering property. This paper suggests a simplified covering transformation of the original covering transformation for extended PLR grammars. The proposed covering transformation reduces the original four rule types to the three rule types.

Surgical Treatment of Corneal Sequestrum with Porcine Urinary Bladder Submucosa Extracellular Matrix (ACeLL Vet® Corneal Disc) in Two Cats

  • Kim, Youngsam;Kang, Seonmi;Nam, Sunhwa;Yun, Seongjin;Seo, Kangmoon
    • Journal of Veterinary Clinics
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    • v.37 no.4
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    • pp.213-216
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    • 2020
  • Two cats were presented to the Dana Animal Hospital Eye Center and were diagnosed with corneal sequestrum through full ophthalmic examination. After lamellar keratectomy using a reusable corneal trephine blade and a crescent microsurgical knife, porcine urinary bladder submucosa extracellular matrix (UBM, ACeLL Vet® corneal disc) was applied to the corneal defects. In both cases, no corneal sequestrum recurrences were observed until 119 days and 253 days after the surgery, respectively. Porcine UBM could be recommended as a surgical scaffold for treatment of corneal sequestrum in cats.

TEM Investigations of Structures and Phase Transitions in Tridymite (투과전자현미경을 이용한 Tridymite의 구조 및 상전이 연구)

  • 김윤중
    • Journal of the Mineralogical Society of Korea
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    • v.15 no.1
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    • pp.44-58
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    • 2002
  • A new polymorph of tridymite, an incommensurately modulated phase (IC phase), has been identified. While the symmetry of the IC lattice is same as that of the Ll phase, the geometry of the IC lattice structure is same as the basis of the L3 structure with a different modulation (modulation vector q=0.22 $c*_{H}$;$\lambda$ 37 ). On the other hand, the characteristic curved diffuse diffration observed from the Ll atoms could occur even at room phase suggests that the dynamic disordering of atoms, especially oxygen atoms could occur even at room temperature. The phase transition of Ll to L3 by grinding is gradual but very conspicuous: LllongrightarrowL1+IClongrightarrowIC+L3longrightarrowL3. However, it is revealed that real transition processes of individual grains are directly related to the local stress fields and preexisting microstructures.

Citron Essential Oils Alleviate the Mediators Related to Rosacea Pathophysiology in Epidermal Keratinocytes

  • Jeon, Hyeon Woo;Na, Eui Young;Yun, Sook Jung;Lee, Seung-Chul;Lee, Jee-Bum
    • Annals of dermatology
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    • v.30 no.6
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    • pp.653-661
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    • 2018
  • Background: Citron is well known for an abundance of antioxidative and anti-inflammatory ingredients such as vitamin C, polyphenol compounds, flavonoids, and limonoids. Objective: In this study, we aimed to evaluate the effects of citron essential oils on rosacea mediators in activated keratinocytes in vitro. Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated with $1{\alpha}$, 25-dihydroxyvitamin $D_3$ ($VD_3$) and interleukin 33 (IL-33) with LL-37 to induce rosacea mediators such as kallikrein 5 (KLK5), cathelicidin, vascular endothelial growth factor (VEGF), and transient receptor potential vanilloid 1 (TRPV1). These mediators were analyzed by performing reverse-transcription polymerase chain reaction (PCR), quantitative real-time PCR, immunocytofluorescence and enzyme-linked immunosorbent assay after NHEKs were treated with citron seed and unripe citron essential oils. Results: The messenger RNA (mRNA) and protein levels of KLK5 and LL-37 induced by $VD_3$ were suppressed by citron seed and unripe citron essential oils. Furthermore, the mRNA and protein levels of VEGF and TRPV1 induced by IL-33 with LL-37 were also suppressed by citron essential oils. Conclusion: These results show that citron essential oils have suppressive effects on rosacea mediators in activated epidermal keratinocytes, which indicates that the citron essential oils may be valuable adjuvant therapeutic agents for rosacea.