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Robert Bissonnette, Judilyn Fuentes-Duculan, Shunya Mashiko, Xuan Li, Kathleen M Bonifacio, Inna Cueto, Mayte Suárez-Fariñas, Catherine Maari, Chantal Bolduc, Simon Nigen, Marika Sarfati, James G Krueger
BACKGROUND: Palmoplantar pustular psoriasis (PPPP) is a variant of psoriasis, which has significant negative impact on quality of life. The cellular and molecular inflammatory pathways involved in PPPP have not been well studied. OBJECTIVE: Study the expression of cytokines and chemokines involved in the IL-17/IL-23 axis in palmoplantar pustular psoriasis and other difficult to treat psoriasis areas (palms, scalp, elbows and lower legs). METHODS: Skin biopsies were performed on a total of 80 patients with PPPP, non-pustular palmoplantar psoriasis (NPPPP), or psoriasis located on elbows, knees and scalp as well as 10 healthy subjects...
September 29, 2016: Journal of Dermatological Science
Mija Ahn, Pethaiah Gunasekaran, Ganesan Rajasekaran, Eun Young Kim, Soo-Jae Lee, Geul Bang, Kun Cho, Jae-Kyung Hyun, Hyun-Ju Lee, Young Ho Jeon, Nam-Hyung Kim, Eun Kyoung Ryu, Song Yub Shin, Jeong Kyu Bang
In this study, we report on the first chemical synthesis of ultra-short pyrazole-arginine based antimicrobial peptidomimetics derived from the newly synthesized N-alkyl/aryl pyrazole amino acids. Through the systematic tuning of hydrophobicity, charge, and peptide length, we identified the shortest peptide Py11 with the most potent antimicrobial activity. Py11 displayed greater antimicrobial activity against antibiotic-resistant bacteria, including MRSA, MDRPA, and VREF, which was approximately 2-4 times higher than that of melittin...
September 23, 2016: European Journal of Medicinal Chemistry
T C Mitulescu, C Stavaru, L M Voinea, L M Banica, C Matache, D Predeteanu
Hypothesis:Abnormal Vitamin D (Vit D) level could have consequences on the immuno-inflammatory processes in Ankylosing Spondylitis (AS). Aim:The purpose of this study was to analyze the role of Vitamin D in the interplay between immune and inflammation effectors in AS associated-Acute Anterior Uveitis (AAU). Methods and Results:25-hydroxyvitamin D (Vit D), LL-37 peptide, IL-8 and Serum Amyloid A (SAA) were identified and quantified in the serum/ plasma of thirty-four AS patients [eleven AS patients presenting AAU (AAU AS patients) and twenty-three AS patients without AAU (wAAU AS patients)] and eighteen healthy individuals (Control) using enzyme-linked immunosorbent assay...
January 2016: Journal of Medicine and Life
Ying Li, Zhenyu Qian, Li Ma, Shuxin Hu, Daguan Nong, Chunhua Xu, Fangfu Ye, Ying Lu, Guanghong Wei, Ming Li
Research on the dynamics of single-membrane proteins remains underdeveloped due to the lack of proper approaches that can probe in real time the protein's insertion depth in lipid bilayers. Here we report a single-molecule visualization method to track both vertical insertion and lateral diffusion of membrane proteins in supported lipid bilayers by exploiting the surface-induced fluorescence attenuation (SIFA) of fluorophores. The attenuation follows a d(-4) dependency, where d is the fluorophore-to-surface distance...
2016: Nature Communications
Alicja Krejner, Małgorzata Litwiniuk, Tomasz Grzela
Human cathelicidin, LL-37, is small antimicrobial peptide, which reveals also some immunomodulatory and proangiogenic properties and, therefore, may promote wound healing. The expression of LL-37 is controlled by various factors, including vitamin D. Thus, any disturbances in vitamin D level may influence LL-37 production and, possibly, affect wound healing. Since deficiency of vitamin D was identified as a common problem in the population, this proof of concept study aimed to verify the relationship between serum levels of LL-37, vitamin D, and healing rate of venous leg ulcers...
September 23, 2016: Archivum Immunologiae et Therapiae Experimentalis
Yi-Jie Guo, Bo Zhang, Xue-Song Feng, Hui-Xun Ren, Ji-Ru Xu
BACKGROUND: Streptococcus mutans forms biofilms as a resistance mechanism against antimicrobial agents in the human oral cavity. We recently showed that human cathelicidin LL-37 exhibits inhibitory effects on biofilm formation of S. mutans through interaction with lipoteichoic acid (LTA), but without antibacterial or biofilm dispersal abilities. (-)-Epigallocatechin gallate (EGCG) is the most abundant constituent of tea catechins that has the greatest anti-infective potential to inhibit the growth of various microorganisms and biofilm formation...
2016: BMC Oral Health
Jessica Z Kubicek-Sutherland, Hava Lofton, Martin Vestergaard, Karin Hjort, Hanne Ingmer, Dan I Andersson
BACKGROUND: The clinical development of antimicrobial peptides (AMPs) is currently under evaluation to combat the rapid increase in MDR bacterial pathogens. However, many AMPs closely resemble components of the human innate immune system and the ramifications of prolonged bacterial exposure to AMPs are not fully understood. OBJECTIVES: We show that in vitro serial passage of a clinical USA300 MRSA strain in a host-mimicking environment containing host-derived AMPs results in the selection of stable AMP resistance...
September 20, 2016: Journal of Antimicrobial Chemotherapy
Jessica A Alvarez, Jocelyn R Grunwell, Scott E Gillespie, Vin Tangpricha, Kiran B Hebbar
Critically ill populations incur high levels of oxidative stress and commonly present with vitamin D deficiency. This study aimed to investigate the relationship between vitamin D status and plasma markers of glutathione (GSH) and cysteine (Cys) redox and immunity in critically ill children. This was a cross-sectional study of n=50 PICU patients. Subjects were categorized according to their plasma 25-hydroxyvitamin D [25(OH)D] concentrations: (<20, 20-30, and ≥30ng/dL). Plasma GSH, glutathione disulfide (GSSG), Cys, and cystine (CySS) were measured with high-performance liquid chromatography, and their associated redox potentials determined (EhGSSG and EhCySS, respectively)...
September 15, 2016: Journal of Steroid Biochemistry and Molecular Biology
Erica Miraglia, Frank Nylén, Katarina Johansson, Elias Arnér, Marcus Cebula, Susan Farmand, Håkan Ottosson, Roger Strömberg, Gudmundur H Gudmundsson, Birgitta Agerberth, Peter Bergman
Bacterial resistance against classical antibiotics is a growing problem and the development of new antibiotics is limited. Thus, novel alternatives to antibiotics are warranted. Antimicrobial peptides (AMPs) are effector molecules of innate immunity that can be induced by several compounds, including vitamin D and phenyl-butyrate (PBA). Utilizing a luciferase based assay, we recently discovered that the histone deacetylase inhibitor Entinostat is a potent inducer of the CAMP gene encoding the human cathelicidin LL-37...
2016: Scientific Reports
Julio E Castañeda-Delgado, Isabel Frausto-Lujan, Irma González-Curiel, Alejandra Montoya-Rosales, Carmen J Serrano, Flor Torres-Juarez, Jose A Enciso-Moreno, Bruno Rivas-Santiago
Aging is a major health issue due to the increased susceptibility of elderly people to infectious, autoimmune, and cardiovascular diseases. Innate immunity is an important mechanism to avoid primary infections; therefore, decreasing of its activity may lead to development of infections. Antimicrobial peptides (AMPs) are effector molecules of innate immunity that can eliminate microbial invaders. The role that cytokines play in the regulation of these innate immune mechanisms needs to be explored. Serum determinations of Th1, Th2, and Th17 cytokines were performed in order to evaluate their association with AMPs human beta-defensin (HBD)-2 and LL-37 in young adults, elder adults, and elder adults with recurrent infections...
September 12, 2016: Immunological Investigations
Simon D Pouwels, Laura Hesse, Alen Faiz, Jaap Lubbers, Priya K Bodha, Nick H T Ten Hacken, Antoon J M van Oosterhout, Martijn C Nawijn, Irene H Heijink
Cigarette smoke (CS) exposure is a major risk factor for COPD. We investigated whether CS-induced DAMP release or DAMP-mediated inflammation contributes to susceptibility for COPD. Samples, including bronchial brushings were collected from young and old individuals, susceptible and non-susceptible for the development of COPD, before and after smoking, and used for gene profiling and airway epithelial cell (AEC) culture. AECs were exposed to CS extract (CSE) or specific DAMPs. BALB/cByJ and DBA/2J mice were intra-nasally exposed to LL-37 and mitochondrial (mt)DAMPs...
September 9, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Eddy-Tim Verjans, Sven Zels, Walter Luyten, Bart Landuyt, Liliane Schoofs
The human cathelicidin peptide LL-37 plays a crucial role in the immune system on many levels, from the first line of defense in epithelial cells to restoring the tissue after infection. On host cells, the majority of the LL-37-induced effects are mediated via the direct or indirect activation of several structurally unrelated cell surface receptors or intracellular targets. How LL-37 is able to affect multiple receptors is currently not well understood. So far, the mechanistic details underlying receptor activation are poorly investigated and evidence for a conventional ligand/receptor interaction is scarce...
September 5, 2016: Peptides
Wei Wang, Jinjing Jia, Changji Li, Qiqi Duan, Jiao Yang, Xin Wang, Ruilian Li, Caifeng Chen, Huling Yan, Yan Zheng
The antimicrobial peptide LL-37 not only contributes to the host defence against microbial invasion but also regulates immune activity, angiogenesis and cell proliferation. Studies have shown that LL-37 participates in the development of a variety of tumours, such as lung cancer, ovarian cancer, breast cancer and melanoma. However, the role of LL-37 in the development of skin squamous cell carcinoma (SCC) is not clear. The present study used immunohistochemistry to confirm that the expression of human DNA-binding protein A (dbpA) was increased in SCC tissues...
September 2016: Oncology Letters
Mark Gontsarik, Matthias T Buhmann, Anan Yaghmur, Qun Ren, Katharina Maniura-Weber, Stefan Salentinig
Designing efficient colloidal systems for the delivery of membrane active antimicrobial peptides requires in-depth understanding of their structural and morphological characteristics. Using dispersions of inverted type bicontinuous cubic phase (cubosomes), we examine the effect of integrating the amphiphilic peptide LL-37 at different concentrations on the self-assembled structure and evaluate its bactericidal ability against Escherichia coli. Small-angle X-ray scattering, dynamic light scattering, and cryogenic transmission electron microscopy show that LL-37 integrates into the bicontinuous cubic structure, inducing colloidal transformations to sponge and lamellar phases and micelles in a concentration-dependent manner...
September 1, 2016: Journal of Physical Chemistry Letters
Paula Fernanda Kreling, Kelly Limi Aida, Loiane Massunari, Karina Sampaio Caiaffa, Célio Percinoto, Telma Blanca Lombardo Bedran, Denise Madalena Palomari Spolidorio, Gabriel Flores Abuna, Eduardo Maffud Cilli, Cristiane Duque
This study evaluated the cytotoxicity and effect of fragments derived from three oral cationic peptides (CP): LL-37, D6-17 and D1-23 against cariogenic bacteria under planktonic and biofilm conditions. For cytotoxicity analysis, two epithelial cell lines were used. The minimum inhibitory concentration and the minimal bactericidal concentration were determined for the CP fragments and the control (chlorhexidine-CHX) against cariogenic bacteria. The fractional inhibitory concentration was obtained for the combinations of CP fragments on Streptococcus mutans...
October 2016: Biofouling
Shanshan Xie, Laura Spelmink, Mario Codemo, Karthik Subramanian, Katrin Pütsep, Birgitta Henriques-Normark, Marie Olliver
The traditional Chinese medicine Chan-Su is widely used for treatment of cancer and cardiovascular diseases, but also as a remedy for infections such as furunculosis, tonsillitis and acute pharyngitis. The clinical use of Chan-Su suggests that it has anti-infective effects, however, the mechanism of action is incompletely understood. In particular, the effect on the human immune system is poorly defined. Here, we describe previously unrecognized immunomodulatory activities of cinobufagin (CBG), a major bioactive component of Chan-Su...
2016: PloS One
Che Chunxiao, Jiang Keyu, Ma Yuanyuan, Zeng Sa, Zhou Jianye, Li Zhiqiang, He Xiangyi
OBJECTIVE: This study aimed to evaluate the biological characteristics of a human specifically targeted antimi- crobial peptide C16LL-37 against Streptococcus mutans (S. mutans). METHODS: In this study, an antimicrobial peptide LL-37, a peptide derived from CSP(C16) (S. mutans competence stimulating peptide), and recombinant peptide C16LL-37 were synthesized by Fmoc-chemistry-based strategy. The selectivity and antibacterial activity of C16LL-37 were identified by the colony counting method on microbial culture plates...
June 2016: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
Srikanth Mairpady Shambat, Nikolai Siemens, Ian R Monk, Disha B Mohan, Santhosh Mukundan, Karthickeyan Chella Krishnan, Sushma Prabhakara, Johanna Snäll, Angela Kearns, Francois Vandenesch, Mattias Svensson, Malak Kotb, Balasubramanian Gopal, Gayathri Arakere, Anna Norrby-Teglund
Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of skin and soft tissue infections. One of the highly successful and rapidly disseminating clones is MRSA ST22 commonly associated with skin tropism. Here we show that a naturally occurring single amino acid substitution (tyrosine to cysteine) at position 223 of AgrC determines starkly different ST22 S. aureus virulence phenotypes, e.g. cytotoxic or colonizing, as evident in both in vitro and in vivo skin infections. Y223C amino acid substitution destabilizes AgrC-AgrA interaction leading to a colonizing phenotype characterized by upregulation of bacterial surface proteins...
2016: Scientific Reports
Midori Doke, Haruka Fukamachi, Hirobumi Morisaki, Takafumi Arimoto, Hideo Kataoka, Hirotaka Kuwata
Periodontitis is an inflammatory disease caused by periodontal bacteria in subgingival plaque. These bacteria are able to colonize the periodontal region by evading the host immune response. Neutrophils, the host's first line of defense against infection, use various strategies to kill invading pathogens, including neutrophil extracellular traps (NETs). NETs are extracellular net-like fibers comprising DNA and antimicrobial components such as histones, LL-37, defensins, myeloperoxidase, and neutrophil elastase from neutrophils that disarm and kill bacteria extracellularly...
August 1, 2016: Molecular Oral Microbiology
Jun-Jun Luan, Guang-Qun Xing
OBJECTIVES: Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) are a group of systemic autoimmune disorders characterized by necrotizing inflammation of small- to medium-sized blood vessels. The pathogenesis of patients with AAV are still in investigation. In this study, we explored the involvement of LL-37 and nucleic acids in AAV. METHODS: 15 patients with AAV diagnosed according to the Chapel Hill definition between October 2014 and July 2015 in the department of Nephrology of Huangdao, affiliated Hospital of Qingdao University were enrolled...
July 30, 2016: Journal of Nephrology
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