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Mary Clark, Jessica Kim, Neelou Etesami, Jacqueline Shimamoto, Ryan V Whalen, Gary Martin, Cheryl Y M Okumura
The resurgence of Group A Streptococcus (GAS) infections in the past two decades has been a rising major public health concern. Due to a large number of GAS infections occurring in the skin, mast cells (MCs), innate immune cells known to localize to the dermis, could play an important role in controlling infection. MCs can exert their antimicrobial activities either early during infection, by degranulation and release of antimicrobial proteases and the cathelicidin-derived antimicrobial peptide LL-37, or by forming antibacterial MC extracellular traps (MCETs) in later stages of infection...
2018: Frontiers in Immunology
Zhanyi Gao, Kaining Liu, Huanxin Meng
BACKGROUND: The vitamin D pathway, from toll-like receptor activation to human cationic antimicrobial protein (hCAP-18/LL-37) generation, has been identified in monocytes and keratinocytes. This study aimed to investigate the vitamin D pathway in human gingival fibroblasts (hGFs) and periodontal ligament cells (hPDLCs) and to provide preliminary evidence of its role in periodontal immune defense. METHODS: Primary cultures of hGFs and hPDLCs were stimulated with 1,25-dihydroxy vitamin D3 and 25-hydroxy vitamin D3 , with or without Porphyromonas gingivalis lipopolysaccharide...
February 18, 2018: Journal of Periodontology
Rafael Taeho Han, Hye Young Kim, Hyun Ryu, Wooyoung Jang, Seung Ha Cha, Hyo Young Kim, JaeHee Lee, Seung Keun Back, Hee Jin Kim, Heung Sik Na
BACKGROUND: Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease associated with hyperreactivity to environmental triggers. Among those, outdoor air pollutants such as particulate matter (PM) have been reported to aggravate pre-existing AD. However, underlying mechanisms of air pollution-induced aggravation of AD have hardly been studied. OBJECTIVE: To investigate the molecular mechanisms by which glyoxal, a PM-forming organic compound, exacerbates the symptoms of AD induced by neonatal capsaicin treatment...
February 21, 2018: Journal of Dermatological Science
Alicia Wong, Danuta Bryzek, Ewelina Dobosz, Carsten Scavenius, Pavel Svoboda, Maria Rapala-Kozik, Adam Lesner, Ivo Frydrych, Jan Enghild, Piotr Mydel, Jan Pohl, Paul R Thompson, Jan Potempa, Joanna Koziel
LL-37, the only human cathelicidin that is released during inflammation, is a potent regulator of immune responses by facilitating delivery of oligonucleotides to intracellular TLR-9, thereby enhancing the response of human plasmacytoid dendritic cells (pDCs) to extracellular DNA. Although important for pathogen recognition, this mechanism may facilitate development of autoimmune diseases. In this article, we show that citrullination of LL-37 by peptidyl-arginine deiminases (PADs) hindered peptide-dependent DNA uptake and sensing by pDCs...
February 23, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Kevin M Claunch, Madeline Bush, Christopher R Evans, Jacob A Malmquist, Matthew C Hale, Shauna M McGillivray
ClpX functions as either an independent chaperone or a component of the ClpXP protease, a conserved intracellular protease that acts as a global regulator in the bacterial cell by degrading regulatory proteins, stress response proteins and rate-limiting enzymes. Previously, we found that loss of clpX in Bacillus anthracis Sterne leads to increased susceptibility to antimicrobial agents that target the cell envelope. The aim of this study was to identify genes within the regulatory network of clpX that contribute to antimicrobial resistance...
February 23, 2018: Microbiology
Francesco Di Virgilio, Anna L Giuliani, Valentina Vultaggio-Poma, Simonetta Falzoni, Alba C Sarti
The P2X7 receptor (P2X7R) is a ligand-gated plasma membrane ion channel belonging to the P2X receptor subfamily activated by extracellular nucleotides. General consensus holds that the physiological (and maybe the only) agonist is ATP. However, scattered evidence generated over the last several years suggests that ATP might not be the only agonist, especially at inflammatory sites. Solid data show that NAD + covalently modifies the P2X7R of mouse T lymphocytes, thus lowering the ATP threshold for activation...
2018: Frontiers in Pharmacology
Sunithi Gunasekera, Taj Muhammad, Adam A Strömstedt, K Johan Rosengren, Ulf Göransson
The human host defence peptide LL-37 is a broad-spectrum antibiotic with immunomodulatory functions. Residues 18-29 in LL-37 have previously been identified as a minimal peptide (KR-12) that retains antibacterial activity with decreased cytotoxicity. In this study, we generated analogues of KR-12 by Ala and Lys scans to identify key elements for activity. These were tested against a panel of human pathogens and for membrane permeabilization on liposomes. Replacements of hydrophobic and cationic residues with Ala were detrimental for antibiotic potency...
February 11, 2018: Chembiochem: a European Journal of Chemical Biology
Daniel Svensson, Alexandra Aidoukovitch, Emma Anders, Birgitta Agerberth, Fredrik Andersson, Eva Ekblad, Dan Ericson, Daniel Nebel, Ulrikke Voss, Bengt-Olof Nilsson
The human host defense peptide, LL-37, is an important player in the first line of defense against invading microorganisms. LL-37 and its precursor, hCAP18, have been detected in unstimulated whole saliva but no reports showing hCAP18/LL-37 in isolated, parotid, and/or submandibular/sublingual saliva have been presented. Here, we measured the levels of hCAP18/LL-37 in human parotid and submandibular/sublingual saliva and investigated the expression of hCAP18/LL-37 in parotid and submandibular gland tissue. Parotid and submandibular/sublingual saliva was collected from healthy volunteers, and the levels of hCAP18/LL-37 in saliva were analyzed by dot blot, ELISA, and western blotting...
February 9, 2018: European Journal of Oral Sciences
E Ramos-Martínez, M R López-Vancell, J C Fernández de Córdova-Aguirre, J Rojas-Serrano, A Chavarría, A Velasco-Medina, G Velázquez-Sámano
BACKGROUND: Vitamin D is a molecule that modulates the immune response and shows anti-inflammatory effects that are beneficial for the control of chronic diseases such as asthma. The trial aim was to explore the effect of vitamin D supplementation on the colonization of pathogenic bacteria in the upper respiratory tract of allergic asthmatic patients. METHODS: This study was conducted in 86 patients between 18 and 50 years of age who were randomly divided into two groups...
February 2, 2018: Cytokine
Min Wan, Xiao Tang, Rokeya Sultana Rekha, S S V Jagadeeswara Rao Muvva, Susanna Brighenti, Birgitta Agerberth, Jesper Z Haeggström
Prostaglandin (PG)E2 is an arachidonic acid-derived lipid mediator that plays an important role in inflammation and immunity. In this study, we demonstrate that PGE2 suppresses basal and 1,25-dihydroxy vitamin D3 (VD3 )-induced expression of hCAP18/LL-37 via E prostanoid (EP)2 and EP4 receptors. In humans, VD3 up-regulates vitamin D receptor (VDR) expression and promotes transcription of the cathelicidin hCAP18/LL-37 gene, whereas PGE2 counteracts this effect. We find that PGE2 induces the cAMP/PKA-signaling pathway and enhances the expression of the inhibitory transcription factor cAMP-responsive modulator/inducible cAMP early repressor, which prevents VDR expression and induction of hCAP18/LL-37 in human macrophages...
January 17, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Kanji Horibe, Akihiro Hosoya, Toru Hiraga, Hiroaki Nakamura
OBJECTIVES: Cathelicidin-related antimicrobial peptide (CRAMP) is an antimicrobial peptide in mice and rats homologous to LL-37 in humans. In addition to its antibacterial activity, CRAMP has various physiological functions by binding to formyl peptide receptor 2 (FPR2). However, the role of these peptides in teeth is unknown. Therefore, we investigated the role of CRAMP and FPR2 in tooth development, reparative dentin formation, and defense response. MATERIAL AND METHODS: First, we examined the localization of CRAMP and FPR2 during tooth development by immunohistochemical analysis...
February 2, 2018: Clinical Oral Investigations
Matthew J Pestrak, Sarah B Chaney, Heather C Eggleston, Sheri Dellos-Nolan, Sriteja Dixit, Shomita S Mathew-Steiner, Sashwati Roy, Matthew R Parsek, Chandan K Sen, Daniel J Wozniak
Pseudomonas aeruginosa causes devastating infections in immunocompromised individuals. Once established, P. aeruginosa infections become incredibly difficult to treat due to the development of antibiotic tolerant, aggregated communities known as biofilms. A hyper-biofilm forming clinical variant of P. aeruginosa, known as a rugose small-colony variant (RSCV), is frequently isolated from chronic infections and is correlated with poor clinical outcome. The development of these mutants during infection suggests a selective advantage for this phenotype, but it remains unclear how this phenotype promotes persistence...
February 2, 2018: PLoS Pathogens
Robert Bucki, Bonita Durnaś, Marzena Wątek, Ewelina Piktel, Katrina Cruz, Przemysław Wolak, Paul B Savage, Paul A Janmey
The response of the human immune system to most bacterial infections results in accumulation of neutrophils at infection sites that release a significant quantity of DNA and F-actin. Both are negatively charged polyelectrolytes that can interact with positively charged host defense molecules such as cathelicidin-delivered LL-37 peptide or other cationic antibiotic agents. Evaluation of the ability of bacterial outgrowth (using luminescence measurements or counting colony-forming units) to form a biofilm (quantified by crystal violet staining) and analysis of the structure of DNA/F-actin network by optical microscopy in human pus samples treated with different antibiotics in combination with plasma gelsolin, DNAse 1, and/or poly-aspartic acid revealed that bactericidal activity of most tested antibacterial agents increases in the presence of DNA/F-actin depolymerizing factors...
2018: Infection and Drug Resistance
Mark Gontsarik, Mahsa Mohammadtaheri, Anan Yaghmur, Stefan Salentinig
The delivery of poorly water-soluble antimicrobial peptides (AMPs) that are sensitive to degradation is a major challenge in the pharmaceutical field. In this study, we design and characterize a pH-sensitive nanocarrier with the potential for delivery of AMPs and their protection from degradation. These nanobiointerfaces are prepared through the self-assembly of oleic acid (OA) with the human cathelicidin LL-37 in excess water. Advanced experimental methods including synchrotron small angle X-ray scattering, cryogenic transmission electron microscopy, and dynamic light scattering were used to characterize the OA/LL-37 self-assemblies and their structural alterations in response to changes in pH and composition...
January 31, 2018: Biomaterials Science
Anna Henningham, Mark R Davies, Satoshi Uchiyama, Nina M van Sorge, Sean Lund, Kelsey T Chen, Mark J Walker, Jason N Cole, Victor Nizet
Classification of streptococci is based upon expression of unique cell wall carbohydrate antigens. All serotypes of group A Streptococcus (GAS; Streptococcus pyogenes), a leading cause of infection-related mortality worldwide, express the group A carbohydrate (GAC). GAC, the classical Lancefield antigen, is comprised of a polyrhamnose backbone with N-acetylglucosamine (GlcNAc) side chains. The immunodominant GlcNAc epitope of GAC is the basis of all rapid diagnostic testing for GAS infection. We previously identified the 12-gene GAC biosynthesis gene cluster and determined that the glycosyltransferase GacI was required for addition of the GlcNAc side chain to the polyrhamnose core...
January 30, 2018: MBio
Maja-Lisa Clausen, H-C Slotved, Karen A Krogfelt, Tove Agner
Decreased levels of antimicrobial peptides (AMPs) in atopic dermatitis (AD) have previously been reported and have been linked to the increased susceptibility to skin infections found in AD patients. This study intents to identify AMPs: hBD-2, hBD-3, RNase7, psoriasin and LL-37 in AD patients and healthy controls, and determine concentrations in consecutive depths of the outer most skin layers. Tape stripping was used on lesional and non-lesional skin. From each skin site, 35 consecutive tape strips were collected and pooled in groups of 5...
January 26, 2018: Scientific Reports
Julia Eliette Goeke, Stefan Kist, Sören Schubert, Reinhard Hickel, Karin Christine Huth, Maximilian Kollmuss
OBJECTIVES: Antimicrobial peptides (AMPs) represent important facets of the immune system controlling infectious diseases. However, pathogens show varying susceptibilities to AMPs. This study investigates the susceptibilities of strains of Streptococcus mutans (SM), Actinomyces naeslundii (AN), and Lactobacillus spp. (LB) towards AMPs and if there are correlations between the appearance of such high-risk strains and clinical caries status. MATERIAL AND METHODS: Plaque samples were collected from patients along with clinical examinations...
January 25, 2018: Clinical Oral Investigations
John J Spencer, Rowan E Pitts, Rachel A Pearson, Lauren B King
Increasing multi-drug resistance (MDR) in Acinetobacter baumannii warrants therapeutic alternatives, and the bactericidal nature of antimicrobial peptides offers a possible approach. In this study, we examined the interaction of cathelicidin antimicrobial peptides (AMPs) WAM-1, a marsupial AMP, and LL-37, a human AMP, with A. baumannii clinical isolates. We characterized the antibiotic resistance of the isolates, the bacteriostatic and bactericidal effects of these AMPs, synergistic activity with antibiotics, and their effects on biofilm formation and dispersal...
January 23, 2018: Pathogens and Disease
Edita Holásková, Petr Galuszka, Alžbeta Mičúchová, Marek Šebela, M Tufan Öz, Ivo Frébort
The peptide LL-37, a component of the human innate immune system, represents a promising drug candidate. In particular, the development of low-cost production platform technology is a critical bottleneck in its use in medicine. In the present study, a viable approach for the LL-37 production in transgenic barley was developed. First, comparative analyses of the effects of different fused peptide epitope tags applicable for accumulation and purification on LL-37 production yield were performed using transient expression in tobacco leaves...
January 25, 2018: Biotechnology Journal
Monika Kumaraswamy, Carter Do, George Sakoulas, Poochit Nonejuie, Guan Woei Tseng, Helen King, Joshua Fierer, Joe Pogliano, Victor Nizet
Endocarditis is a rare but serious manifestation of Listeria monocytogenes (LM). However, the optimal treatment strategy for LM endocarditis has yet to be established. Current antibiotic strategies for listeriosis include penicillin G or ampicillin (AMP) monotherapy, or AMP + gentamicin combination therapy which is often favored for endocarditis. The primary objective of our investigation was to assess the utility of AMP + ceftriaxone (CRO) and AMP + daptomycin (DAP) against LM, modeling less nephrotoxic antibiotic combinations traditionally used to manage resistant enterococcal endocarditis...
January 11, 2018: International Journal of Antimicrobial Agents
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