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Awa R N'Diaye, Camille Leclerc, Takfarinas Kentache, Julie Hardouin, Cecile Duclairoir Poc, Yoan Konto-Ghiorghi, Sylvie Chevalier, Olivier Lesouhaitier, Marc G J Feuilloley
Staphylococci can sense Substance P (SP) in skin, but this molecule is generally released by nerve terminals along with another neuropeptide, Calcitonin Gene Related Peptide (CGRP). In this study, we investigated the effects of αCGRP on Staphylococci. CGRP induced a strong stimulation of Staphylococcus epidermidis virulence with a low threshold (<10(-12 )M) whereas Staphylococcus aureus was insensitive to CGRP. We observed that CGRP-treated S. epidermidis induced interleukin 8 release by keratinocytes...
October 14, 2016: Scientific Reports
Hitokazu Esaki, Patrick M Brunner, Yael Renert-Yuval, Tali Czarnowicki, Thy Huynh, Gary Tran, Sarah Lyon, Giselle Rodriguez, Supriya Immaneni, Donald B Johnson, Bruce Bauer, Judilyn Fuentes-Duculan, Xiuzhong Zheng, Xiangyu Peng, Yeriel D Estrada, Hui Xu, Christina de Guzman Strong, Mayte Suárez-Fariñas, James G Krueger, Amy S Paller, Emma Guttman-Yassky
BACKGROUND: Atopic dermatitis (AD) affects 15% to 25% of children and 4% to 7% of adults. Paradigm-shifting discoveries about AD have been based on adult biomarkers, reflecting decades of disease activity, although 85% of cases begin by 5 years. Blood phenotyping shows only TH2 skewing in patients with early-onset pediatric AD, but alterations in early pediatric skin lesions are unknown, limiting advancement of targeted therapies. OBJECTIVE: We sought to characterize the early pediatric AD skin phenotype and its differences from pediatric control subjects and adults with AD...
September 15, 2016: Journal of Allergy and Clinical Immunology
Octavio Ramos-Espinosa, Sujhey Hernández-Bazán, Alejandro Francisco-Cruz, Dulce Mata-Espinosa, Jorge Barrios-Payán, Brenda Marquina-Castillo, Fernando López-Casillas, Marta Carretero, Marcela Del Río, Rogelio Hernández-Pando
Mycobacterium tuberculosis (Mtb) latent infection can lead to reactivation. The design of new strategies to prevent it is an important subject. B6D2F1 mice were infected intratracheally with a low dose of Mtb H37Rv to induce chronic infection. After 7 months, mice were treated with one dose of recombinant adenoviruses encoding TNFα, β defensin-3 and LL37. Immunosupression was induced 1 month later with corticosterone. In comparison with the control group, mice treated with adenoviruses showed significantly less bacterial load and pneumonia, the adenoviruses encoding TNFα and LL37 being the most efficient...
October 2016: Pathogens and Disease
Hang Yang, Mona Helena Biermann, Jan Markus Brauner, Yi Liu, Yi Zhao, Martin Herrmann
Recent data suggest that NETosis plays a crucial role in the innate immune response and disturbs the homeostasis of the immune system. NETosis is a form of neutrophil-specific cell death characterized by the release of large web-like structures referred to as neutrophil extracellular traps (NETs). NETs are composed of DNA strands associated with histones and decorated with about 20 different proteins, including neutrophil elastase, myeloperoxidase, cathepsin G, proteinase 3, high mobility group protein B1, and LL37...
2016: Frontiers in Immunology
Amrollah Sharifi, Mohammad Javad Hosseinzadeh-Attar, Homayoon Vahedi, Saharnaz Nedjat
BACKGROUND: Inflammatory bowel disease (IBD) is an intestinal chronic inflammatory condition and includes Crohn's disease (CD) and ulcerative colitis (UC). It has been proposed that Vitamin D supplementation may have a beneficial role in IBD. AIM: To characterize the effects of Vitamin D on cathelicidin (hCAP/LL37) gene expression, ESR, and serum hs-CRP levels. MATERIALS AND METHODS: Ninety UC patients on remission were randomized to receive 300,000 IU intramuscular Vitamin D or 1 mL normal saline as placebo, respectively...
July 2016: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
Seoyeon Kim, Soonsil Hyun, Yuri Lee, Yan Lee, Jaehoon Yu
Cell-penetrating peptides (CPPs) often have cationic and amphipathic characteristics that are commonly associated with α-helical peptides. These features give CPPs both membrane demolishing and penetrating abilities. To make CPPs safe for biomedical applications, their toxicities resulting from their membrane demolishing abilities must be removed while their cell penetrating abilities must be retained. In this study, we systematically constructed mutants of the amphipathic α-helical model peptide (LKKLLKLLKKLLKLAG, LK peptide)...
September 12, 2016: Biomacromolecules
Ling-Juan Zhang, George L Sen, Nicole L Ward, Andrew Johnston, Kimberly Chun, Yifang Chen, Christopher Adase, James A Sanford, Nina Gao, Melanie Chensee, Emi Sato, Yi Fritz, Jaymie Baliwag, Michael R Williams, Tissa Hata, Richard L Gallo
Type 1 interferons (IFNs) promote inflammation in the skin but the mechanisms responsible for inducing these cytokines are not well understood. We found that IFN-β was abundantly produced by epidermal keratinocytes (KCs) in psoriasis and during wound repair. KC IFN-β production depended on stimulation of mitochondrial antiviral-signaling protein (MAVS) by the antimicrobial peptide LL37 and double stranded-RNA released from necrotic cells. MAVS activated downstream TBK1 (TANK-Binding Kinase 1)-AKT (AKT serine/threonine kinase 1)-IRF3 (interferon regulatory factor 3) signaling cascade leading to IFN-β production and then promoted maturation of dendritic cells...
July 19, 2016: Immunity
Jenny E Han, Jennifer L Jones, Vin Tangpricha, Mona A Brown, Lou Ann S Brown, Li Hao, Gautam Hebbar, Moon Jeong Lee, Shuling Liu, Thomas R Ziegler, Greg S Martin
BACKGROUND: There is a high prevalence of vitamin D deficiency in the critically ill patient population. Several intensive care unit studies have demonstrated an association between vitamin D deficiency [25-hydroxyvitamin D (25(OH)D) < 20 ng/mL] and increased hospital length of stay (LOS), readmission rate, sepsis and mortality. MATERIAL AND METHODS: Pilot, double blind randomized control trial conducted on mechanically ventilated adult ICU patients. Subjects were administered either placebo, 50,000 IU vitamin D3 or 100,000 IU vitamin D3 daily for 5 consecutive days enterally (total vitamin D3 dose = 250,000 IU or 500,000 IU, respectively)...
June 2016: Journal of Clinical & Translational Endocrinology
Xu-Biao Wei, Ru-Juan Wu, Da-Yong Si, Xiu-Dong Liao, Lu-Lu Zhang, Ri-Jun Zhang
Hybridizing different antimicrobial peptides (AMPs) is a particularly successful approach to obtain novel AMPs with increased antimicrobial activity but minimized cytotoxicity. The hybrid peptide cecropin A (1-8)-LL37 (17-30) (C-L) combining the hydrophobic N-terminal fragment of cecropin A (C) with the core antimicrobial fragment of LL37 (L) was designed and synthesized. C-L showed higher antibacterial activity against all indicator strains than C and L, and no hemolytic activity to sheep erythrocytes was observed...
2016: International Journal of Molecular Sciences
Siwei Xiao, Yanyun Gao, Xiaolong Wang, Wei Shen, Jinjia Wang, Xiangshan Zhou, Menghao Cai, Yuanxing Zhang
Although the human antimicrobial peptide LL37 has a broad spectrum of antimicrobial activities, it easily damages host cells following heterologous expressions. This study attempted two strategies to alleviate its damage to host cells when expressed in Pichia pastoris using the AOX1 promoter. Tandem repeat multimers of LL37 were first designed, and secretion expression strains GS115-9 K-(DPLL37DP)n (n = 2, 4, 6 and 8) containing different copies of the LL37 gene were constructed. However, LL37 tandems still killed the cells after 96 h of induction...
June 27, 2016: Preparative Biochemistry & Biotechnology
Jee-Bum Lee, Soo Hyeon Bae, Ki Rang Moon, Eui Young Na, Sook Jung Yun, Seung-Chul Lee
BACKGROUND: Cathelicidin (LL-37), Toll-like receptor 2 (TLR 2), and kallikreins (KLKs) are key inflammatory mediators in rosacea. Laser or light-based devices have been successfully used for rosacea. OBJECTIVE: We investigated the effects of light-emitting diodes (LED) on LL-37, KLKs, TLR 2, and protease activity in cultured normal human epidermal keratinocytes(NHEKs) and rosacea-like mouse skin(RLMS). METHODS: LL-37, KLK 5, KLK 7, and vitamin D receptor were induced by 1α,25-dihydroxyvitaminD3 (VD3 ) and TLR 2 by Ad-CMV transfection in cultured NHEKs...
June 17, 2016: Experimental Dermatology
Miral Fumakia, Emmanuel A Ho
Wound care is a serious healthcare concern, often complicated by prolonged inflammation and bacterial infection, which contributes significantly to mortality and morbidity. Agents commonly used to treat chronic wound infections are limited due to toxicity of the therapy, multifactorial etiology of chronic wounds, deep skin infections, lack of sustained controlled delivery of drugs, and development of drug resistance. LL37 is an endogenous host defense peptide possessing antimicrobial activity and is involved in the modulation of wound healing...
July 5, 2016: Molecular Pharmaceutics
Alexander Stephan, Marina Batinica, Julia Steiger, Pia Hartmann, Frank Zaucke, Wilhelm Bloch, Mario Fabri
As part of the innate host response neutrophils release neutrophil extracellular traps (NETs), protein:DNA complexes that contain a number of antimicrobial peptides (AMPs), such as cathelicidin. Human cathelicidin in its active form, LL37, has potent antimicrobial activity against bacteria. However, whether LL37 derived from NETs contributes to antimicrobial activity against intracellular pathogens remains unclear. Here, we report that NETs induced by mycobacteria contain cathelicidin. Human macrophages internalized NET-bound cathelicidin, which is transported to lysosomal compartments...
August 2016: Immunology
Dae Woong Song, Shin Hwan Kim, Hyung Hwan Kim, Ki Hoon Lee, Chang Seok Ki, Young Hwan Park
UNLABELLED: An antimicrobial peptide motif (Cys-KR12) originating from human cathelicidin peptide (LL37) was immobilized onto electrospun SF nanofiber membranes using EDC/NHS and thiol-maleimide click chemistry to confer the various bioactivities of LL37 onto the membrane for wound care purposes. Surface characterizations revealed that the immobilization density of Cys-KR12 on SF nanofibers could be precisely controlled with a high reaction yield. The Cys-KR12-immobilized SF nanofiber membrane exhibited antimicrobial activity against four pathogenic bacterial strains (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa) without biofilm formation on the membrane surface...
July 15, 2016: Acta Biomaterialia
Hong Jiang, Ludan Liang, Jing Qin, Yingying Lu, Bingjue Li, Yucheng Wang, Chuan Lin, Qin Zhou, Shi Feng, Shun H Yip, Feng Xu, En Yin Lai, Junwen Wang, Jianghua Chen
IgA nephropathy(IgAN) is the most common primary glomerular disease in China. Primary infections always occur before IgAN. However, the pathology of IgAN is still unclear. Previously we found that LL37, a protein secreted by senescent cells, was specific for the progression of IgAN, and also played a role in the neutrophil function. So we hypothesized that the infiltration of neutrophils, inflammation factors, and aging markers , which were modulated by functional networks, induced the immune response and renal injury...
June 7, 2016: Oncotarget
Margaret E Cassin, Andrew J Ford, Sophia M Orbach, Scott E Saverot, Padmavathy Rajagopalan
UNLABELLED: The design of antimicrobial membranes and thin films are critical for the design of biomaterials that can combat bacterial contamination. Since the long-term use of conventional antibiotics can result in bacterial resistance, there is a critical need to incorporate natural antimicrobial peptides (AMPs) that not only prevent a wide range of pathogens from causing infections but can also promote many beneficial outcomes in wounded tissues. We report the design and antimicrobial properties of detachable collagen (COL)/hyaluronic acid (HA) polyelectrolyte multilayers (PEMs) modified with LL-37, a naturally occurring human AMP...
August 2016: Acta Biomaterialia
T Takahashi, Y Asano, K Nakamura, T Yamashita, R Saigusa, Y Ichimura, T Toyama, T Taniguchi, A Yoshizaki, Z Tamaki, Y Tada, M Sugaya, T Kadono, S Sato
BACKGROUND: LL-37 is an antimicrobial peptide with pleiotropic effects on immune system, angiogenesis, and tissue remodeling, which are cardinal pathological events in systemic sclerosis (SSc). OBJECTIVES: To elucidate the potential role of LL-37 in SSc. METHODS: The expression of target molecules was evaluated by immunostaining and quantitative reverse transcription-real time PCR in human and murine skin. The mechanisms regulating LL-37 expression in endothelial cells were examined by gene silencing technique and chromatin immunoprecipitation...
April 23, 2016: British Journal of Dermatology
Itxaso Garcia-Orue, Garazi Gainza, Cecilia Girbau, Rodrigo Alonso, José Javier Aguirre, José Luis Pedraz, Manoli Igartua, Rosa Maria Hernandez
The LL37 is a human antimicrobial peptide which not only has a broad spectrum of antimicrobial activity, but it has also been proved to modulate wound healing by participating in angiogenesis, epithelial cell migration and proliferation, and immune response. In this work, LL37 has been encapsulated in nanostructured lipid carriers (NLCs), produced by the melt-emulsification method, in order to improve its effectiveness. The characterisation of the NLC-LL37 showed a mean size of 270nm, a zeta potential of -26mV and an encapsulation efficiency of 96...
April 11, 2016: European Journal of Pharmaceutics and Biopharmaceutics
Venkata Sanjeev Kumar Neela, Kamakshi Prudhula Devalraju, Satya Sudheer Pydi, Sharada Ramaseri Sunder, Kameswara Rao Adiraju, Surya Satyanarayana Singh, M P J S Anandaraj, Vijaya Lakshmi Valluri
BACKGROUND: Immunological characterization of mycobacterial peptides may help not only in the preparation of a vaccine for leprosy but also in developing in vitro T-cell assays that could perhaps be used as an in vitro correlate for treatment outcome. The main goal of this study was to evaluate the use of Mycobacterium bovis recombinant 32-kDa protein (r32-kDa) antigen-stimulated T-cell assay as a surrogate marker for treatment outcome and monitor vitamin D receptor (VDR)-mediated anti-microbial responses during multidrug therapy (MDT) in leprosy...
September 2016: International Immunology
David O Ulaeto, Christopher J Morris, Marc A Fox, Mark Gumbleton, Konrad Beck
We have previously examined the mechanism of antimicrobial peptides on the outer membrane of vaccinia virus. We show here that the formulation of peptides LL37 and magainin-2B amide in polysorbate 20 (Tween 20) results in greater reductions in virus titer than formulation without detergent, and the effect is replicated by substitution of polysorbate 20 with high-ionic-strength buffer. In contrast, formulation with polysorbate 20 or high-ionic-strength buffer has the opposite effect on bactericidal activity of both peptides, resulting in lesser reductions in titer for both Gram-positive and Gram-negative bacteria...
April 2016: Antimicrobial Agents and Chemotherapy
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