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Ll-37

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https://www.readbyqxmd.com/read/28231019/pro-inflammatory-cytokines-impair-vitamin-d-induced-host-defense-in-cultured-airway-epithelial-cells
#1
Jasmijn A Schrumpf, Gimano D Amatngalim, Joris B Veldkamp, Renate M Verhoosel, Dennis K Ninaber, Soledad R Ordonez, Anne M van der Does, Henk P Haagsman, Pieter S Hiemstra
Vitamin D is a regulator of host defense against infections and induces expression of the antimicrobial peptide hCAP18/LL-37. Vitamin D deficiency is associated with chronic inflammatory lung diseases and respiratory infections. However, it is incompletely understood if and how (chronic) airway inflammation affects vitamin D metabolism and action. We hypothesized that long-term exposure of primary bronchial epithelial cells (PBEC) to pro-inflammatory cytokines alters their vitamin D metabolism, antibacterial activity and expression of hCAP18/LL-37...
February 23, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28228596/antimicrobials-from-human-skin-commensal-bacteria-protect-against-staphylococcus-aureus-and-are-deficient-in-atopic-dermatitis
#2
Teruaki Nakatsuji, Tiffany H Chen, Saisindhu Narala, Kimberly A Chun, Aimee M Two, Tong Yun, Faiza Shafiq, Paul F Kotol, Amina Bouslimani, Alexey V Melnik, Haythem Latif, Ji-Nu Kim, Alexandre Lockhart, Keli Artis, Gloria David, Patricia Taylor, Joanne Streib, Pieter C Dorrestein, Alex Grier, Steven R Gill, Karsten Zengler, Tissa R Hata, Donald Y M Leung, Richard L Gallo
The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing Staphylococcus aureus, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against S. aureus was performed on isolates of coagulase-negative Staphylococcus (CoNS) collected from the skin of healthy and AD subjects...
February 22, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28218580/circulating-cathelicidin-ll-37-in-adult-patients-with-pulmonary-infectious-diseases
#3
Karol Majewski, Paulina Żelechowska, Ewa Brzezińska-Błaszczyk
PURPOSE: The antimicrobial peptide cathelicidin LL-37 plays a role in the immune response in the course of lung infections; however, the exact role of LL-37 in defense mechanisms against bacteria within the respiratory tract is has not been precisely described. The aim of our study was to evaluate LL-37 concentrations in the serum of pulmonary tuberculosis (TB) patients, patients with pneumonia caused by Gram-positive and Gram-negative bacteria and to compare them with those of healthy subjects...
February 19, 2017: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
https://www.readbyqxmd.com/read/28195066/successful-therapy-of-clostridium-difficile-infection-with-fecal-microbiota-transplantation
#4
P C Konturek, J Koziel, W Dieterich, D Haziri, S Wirtz, I Glowczyk, K Konturek, M F Neurath, Y Zopf
Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea and represents an important burden for healthcare worldwide. Symptoms of severe CDI include watery, foul-smelling diarrhea, peripheral leucocytosis, increased C-reactive protein (CRP), acute renal failure, hypotension and pseudomembranous colitis. Recent studies indicate that the main cause of CDI is dysbiosis, an imbalance in the normal gut microbiota. The restoration of a healthy gut microbiota composition via fecal microbiota transplantation (FMT) recently became more popular...
December 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28178190/high-specific-selectivity-and-membrane-active-mechanism-of-synthetic-cationic-hybrid-antimicrobial-peptides-based-on-the-peptide-fv7
#5
Tingting Tan, Di Wu, Weizhong Li, Xin Zheng, Weifen Li, Anshan Shan
Hybrid peptides integrating different functional domains of peptides have many advantages, such as remarkable antimicrobial activity, lower hemolysis and ideal cell selectivity, compared with natural antimicrobial peptides. FV7 (FRIRVRV-NH₂), a consensus amphiphilic sequence was identified as being analogous to host defense peptides. In this study, we designed a series of hybrid peptides FV7-LL-37 (17-29) (FV-LL), FV7-magainin 2 (9-21) (FV-MA) and FV7-cecropin A (1-8) (FV-CE) by combining the FV7 sequence with the small functional sequences LL-37 (17-29) (LL), magainin 2 (9-21) (MA) and cecropin A (1-8) (CE) which all come from well-described natural peptides...
February 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28169482/using-diphenylphosphoryl-azide-dppa-for-the-facile-synthesis-of-biodegradable-antiseptic-random-copolypeptides
#6
Yuji Pu, Yu Du, Mya Mya Khin, Vikashini Ravikumar, Scott A Rice, Hongwei Duan, Mary B Chan-Park
A facile method has been developed for the large-scale synthesis of random copolypeptides composed of multiple (i.e., cationic, hydrophobic, and hydrophilic) amino acids and their relative ratios have been optimized for broad-spectrum antibacterial effect. The copolypeptides obtained have measured compositions close to the design ratios in spite of the differing reactivities of the different amino acids. An optimized random copolypeptide of lysine, leucine, and serine (denoted as KLS-3) mimicking the composition of LL-37 host defense peptide gives broad spectrum antibacterial activity against clinically relevant Gram-negative and Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAO1) with minimum inhibitory concentrations (MICs) of 32-64 μg mL(-1) , as well as good MICs against multidrug resistant Gram-negative bacteria of Escherichia coli EC 958 (64 μg mL(-1) ) and Klebseilla pneumoniae PTR3 (128 μg mL(-1) )...
February 7, 2017: Macromolecular Rapid Communications
https://www.readbyqxmd.com/read/28161291/ll-37-derived-membrane-active-fk-13-analogs-possessing-cell-selectivity-anti-biofilm-activity-and-synergy-with-chloramphenicol-and-anti-inflammatory-activity
#7
Ganesan Rajasekaran, Eun Young Kim, Song Yub Shin
Although the human-derived antimicrobial peptide (AMP) LL-37 has potent antimicrobial and anti-inflammatory activities, its therapeutic application is limited by its low cell selectivity and high production cost due to its large size. To overcome these problems, we tried to develop novel LL-37-derived short α-helical AMPs with improved cell selectivity and without a significant loss of anti-inflammatory activity relative to that of parental LL-37. Using amino acid substitution, we designed and synthesized a series of FK13 analogs based on the sequence of the 13-meric short FK13 peptide (residues 17-29 of LL-37) that has been identified as the region responsible for the antimicrobial activity of LL-37...
February 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28111615/the-effects-of-first-line-anti-tuberculosis-drugs-on-the-actions-of-vitamin-d-in-human-macrophages
#8
Supavit Chesdachai, Susu M Zughaier, Li Hao, Russell R Kempker, Henry M Blumberg, Thomas R Ziegler, Vin Tangpricha
Tuberculosis (TB) is a major global health problem. Patients with TB have a high rate of vitamin D deficiency, both at diagnosis and during the course of treatment with anti-tuberculosis drugs. Although data on the efficacy of vitamin D supplementation on Mycobacterium tuberculosis (Mtb) clearance is uncertain from randomized controlled trials (RCTs), vitamin D enhances the expression of the anti-microbial peptide human cathelicidin (hCAP18) in cultured macrophages in vitro. One possible explanation for the mixed (primarily negative) results of RCTs examining vitamin D treatment in TB infection is that anti-TB drugs given to enrolled subjects may impact actions of vitamin D to enhance cathelicidin in macrophages...
December 2016: Journal of Clinical & Translational Endocrinology
https://www.readbyqxmd.com/read/28102367/interspecies-cathelicidin-comparison-reveals-divergence-in-antimicrobial-activity-tlr-modulation-chemokine-induction-and-regulation-of-phagocytosis
#9
Maarten Coorens, Maaike R Scheenstra, Edwin J A Veldhuizen, Henk P Haagsman
Cathelicidins are short cationic peptides initially described as antimicrobial peptides, which can also modulate the immune system. Because most findings have been described in the context of human LL-37 or murine CRAMP, or have been investigated under varying conditions, it is unclear which functions are cathelicidin specific and which functions are general cathelicidin properties. This study compares 12 cathelicidins from 6 species under standardized conditions to better understand the conservation of cathelicidin functions...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097645/bacterial-subversion-of-camp-signalling-inhibits-cathelicidin-expression-which-is-required-for-innate-resistance-to-mycobacterium-tuberculosis
#10
Shashank Gupta, Kathryn Winglee, Richard Gallo, William R Bishai
Antimicrobial peptides such as cathelicidins are an important component of innate immune defence against inhaled microorganisms and have demonstrated antimicrobial activity against Mycobacterium tuberculosis with in vitro models. Despite this, little is known about the regulation and expression of cathelicidin during tuberculosis in vivo. We sought to determine whether the cathelicidin-related antimicrobial peptide (Cramp) gene, the murine functional homologue of the human cathelicidin gene (CAMP or LL-37), is required for regulating protective immunity during M...
January 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28089718/cathelicidin-antimicrobial-peptide-from-alligator-mississippiensis-has-antibacterial-activity-against-multi-drug-resistant-acinetobacter-baumanii-and-klebsiella-pneumoniae
#11
Stephanie M Barksdale, Evelyn J Hrifko, Monique L van Hoek
Alligator mississippiensis (American alligator), a member of order Crocodilia, lives in bacteria-laden environments but is not often known to succumb to bacterial infections. Their serum has been shown to have antibacterial activity beyond that of human serum, and it is believed that this activity is partially due to cationic antimicrobial peptides (CAMPs). CAMPs are produced by many organisms as part of the innate immune system. CAMPs are attractive possible therapies against multi-drug resistant bacteria, such as those found in biofilm-infected war wounds, because they seldom cause genetic resistance in bacteria and are effective against antibiotic resistant bacteria...
January 13, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28069814/muc2-mucin-and-butyrate-contribute-to-the-synthesis-of-the-antimicrobial-peptide-cathelicidin-in-response-to-e-histolytica-and-dss-induced-colitis
#12
Eduardo R Cobo, Vanessa Kissoon-Singh, France Moreau, Ravi Holani, Kris Chadee
Embedded in the colonic mucus are cathelicidins, small cationic peptides secreted by colonic epithelial cells. Humans and mice have one cathelicidin-related antimicrobial peptide (CRAMP), LL-37/hCAP-18 and Cramp respectively, with related structure and functions. Altered production of MUC2 mucin and antimicrobial peptides is characteristic of intestinal amebiasis. The interactions between MUC2 mucin and cathelicidins in conferring innate immunity against Entamoeba histolytica (Eh) are not well characterized...
January 9, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28064019/the-random-co-polymer-glatiramer-acetate-rapidly-kills-primary-human-leukocytes-through-sialic-acid-dependent-cell-membrane-damage
#13
Stig Hill Christiansen, Xianwei Zhang, Kristian Juul-Madsen, Michael Lykke Hvam, Brian Stougaard Vad, Manja Annette Behrens, Ida Lysgaard Thygesen, Babak Jalilian, Jan Skov Pedersen, Kenneth A Howard, Daniel E Otzen, Thomas Vorup-Jensen
The formulation glatiramer acetate (GA) is widely used in therapy of multiple sclerosis. GA consists of random copolymers of four amino acids, in ratios that produce a predominantly positive charge and an amphipathic character. With the extraordinary complexity of the drug, several pharmacological modes-of-action were suggested, but so far none, which rationalizes the cationicity and amphipathicity as part of the mode-of-action. Here, we report that GA rapidly kills primary human T lymphocytes and, less actively, monocytes...
January 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28061765/mir-663a-regulates-growth-of-colon-cancer-cells-after-administration-of-antimicrobial-peptides-by-targeting-cxcr4-p21-pathway
#14
Kengo Kuroda, Tomokazu Fukuda, Marija Krstic-Demonacos, Constantinos Demonacos, Kazuhiko Okumura, Hiroshi Isogai, Miwa Hayashi, Kazuki Saito, Emiko Isogai
BACKGROUND: Antimicrobial peptides (AMPs) play important roles in the innate immune system of all life forms and recently have been characterized as multifunctional peptides that have a variety of biological roles such as anticancer agents. However, detailed mechanism of antimicrobial peptides on cancer cells is still largely unknown. METHODS: miRNA array and real-time qPCR were performed to reveal the behavior of miRNA in colon cancer HCT116 cells during the growth suppression induced by the AMPs...
January 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28038684/ll-37-boosts-immunosuppressive-function-of-placenta-derived-mesenchymal-stromal-cells
#15
Martha Oliveira-Bravo, Bruno Braga Sangiorgi, Josiane Lilian Dos Santos Schiavinato, Juliana Lott Carvalho, Dimas Tadeu Covas, Rodrigo Alexandre Panepucci, Francisco de Assis Rocha Neves, Octávio Luiz Franco, Rinaldo Wellerson Pereira, Felipe Saldanha-Araujo
BACKGROUND: Although promising for graft-versus-host disease (GvHD) treatment, MSC therapy still faces important challenges. For instance, increasing MSC migratory capacity as well as potentializing immune response suppression are of interest. For GvHD management, preventing opportunistic infections is also a valuable strategy, since immunocompromised patients are easy targets for infections. LL-37 is a host defense peptide (HDP) that has been deeply investigated due to its immunomodulatory function...
December 30, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28013511/assays-for-identifying-inducers-of-the-antimicrobial-peptide-ll-37
#16
Frank Nylén, Peter Bergman, Gudmundur H Gudmundsson, Birgitta Agerberth
One promising approach to meet the growing problem of antibiotic resistance is to modulate host defense mechanisms, i.e., host-directed therapy (HDT), in the fight against infections. Induction of endogenous antimicrobial peptides (AMPs) via small molecular compounds, such as 1,25-dihydroxyvitamin D3 or phenylbutyrate, could provide one such HDT-based approach.We have developed a cell-based screening assay for the identification of novel compounds with the capacity to induce AMP expression and here follows the detailed protocol...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28012697/the-host-defense-peptide-ll-37-a-possible-inducer-of-the-type-i-interferon-system-in-patients-with-polymyositis-and-dermatomyositis
#17
Xin Lu, Quan Tang, Monica Lindh, Maryam Dastmalchi, Helene Alexanderson, Karin Popovic Silwerfeldt, Birgitta Agerberth, Ingrid E Lundberg, Cecilia Wick
The type I interferon (IFN) system has recently been suggested to play important and essential roles in the pathogenesis of myositis. However, a clarification of how type I IFNs could function as triggering factor(s) in the pathogenesis of myositis has yet failed. Through activation of the type I IFN system, the host defense peptide LL-37 carries numerous immunomodulatory properties and is implicated in the pathogenesis of several other autoimmune diseases, including systemic lupus erythematosus (SLE). The expression of LL-37 can be regulated by various endogenous factors including the active form of vitamin D (25(OH)D3)...
December 22, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28006672/gene-electrotransfer-into-skin-using-noninvasive-multi-electrode-array-for-vaccination-and-wound-healing
#18
Spela Kos, Kevin Vanvarenberg, Tanja Dolinsek, Maja Cemazar, Jure Jelenc, Véronique Préat, Gregor Sersa, Gaëlle Vandermeulen
Skin is an attractive target for gene electrotransfer due to its easy accessibility and its interesting immune properties. Since electrodes are often invasive and frequently induce discomfort during pulse application, there is a fundamental need for non-invasive electrodes for skin delivery. We developed circular pin non-invasive multi-electrode array (MEA), suitable for different clinical applications. MEA was first employed to deliver a luciferase reporter gene. Then, it was used to deliver a DNA vaccine coding for ovalbumin or a plasmid encoding hCAP-18/LL-37 for promoting wound healing...
April 2017: Bioelectrochemistry
https://www.readbyqxmd.com/read/27997347/mirolysin-a-lysarginase-from-tannerella-forsythia-proteolytically-inactivates-the-human-cathelicidin-ll-37
#19
Lahari Koneru, Miroslaw Ksiazek, Irena Waligorska, Anna Straczek, Magdalena Lukasik, Mariusz Madej, Ida B Thøgersen, Jan J Enghild, Jan Potempa
Tannerella forsythia is a periodontal pathogen expressing six secretory proteolytic enzymes with a unique multidomain structure referred to as KLIKK proteases. Two of these proteases, karilysin and mirolysin, were previously shown to protect the bacterium against complement-mediated bactericidal activity. The latter metalloprotease, however, was not characterized at the protein level. Therefore, we purified recombinant mirolysin and subjected it to detailed biochemical characterization. Mirolysin was obtained as a 66 kDa zymogen, which autoproteolytically processed itself into a 31 kDa active form via truncations at both the N- and C-termini...
December 20, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27994673/antimicrobial-peptide-ll-37-participates-in-the-transcriptional-regulation-of-melanoma-cells
#20
Mindy Muñoz, Madeleine Craske, Patricia Severino, Thais Martins de Lima, Paul Labhart, Roger Chammas, Irineu Tadeu Velasco, Marcel Cerqueira César Machado, Brian Egan, Helder I Nakaya, Fabiano Pinheiro da Silva
Antimicrobial peptides are an ancient family of molecules that emerged millions of years ago and have been strongly conserved during the evolutionary process of living organisms. Recently, our group described that the human antimicrobial peptide LL-37 migrates to the nucleus, raising the possibility that LL-37 could directly modulate transcription under certain conditions. Here, we showed evidence that LL-37 binds to gene promoter regions, and LL-37 gene silencing changed the transcriptional program of melanoma A375 cells genes associated with histone, metabolism, cellular stress, ubiquitination and mitochondria...
2016: Journal of Cancer
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