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Ting Zhang, Hao Zhang, Liang He, Zhihong Wang, Wenwu Dong, Wei Sun, Ping Zhang
BACKGROUND Low levels of 1-25-dihydroxyvitamin D3 [1,25(OH)2D3] in serum may be a risk factor for several tumor types. Also, high cathelicidin antimicrobial peptide (CAMP) expression is regarded to be important against tumor progression. We evaluated the potential importance of 1,25(OH)2D3 in the diagnosis and treatment of papillary thyroid cancer (PTC). MATERIAL AND METHODS The preoperative serum level of 1,25(OH)2D3 was measured using a double-antibody sandwich enzyme-linked immunosorbent assay. Vitamin D3 receptor (VDR) expression was detected by streptavidin-peroxidase immunohistochemical staining in PTC specimens...
March 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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
Alphonse Garcia
Small viral proteins with cationic domains can be involved in multiple biological processes including cell penetration or interaction with intracellular targets. Within the last two decades several reports indicated that the C-terminus of HIV-1 Vpr is a cell penetrating sequence, a PP2A-dependent death domain and also displays toxicity against Gram-negative E. coli. Interestingly, HIV-1 Vpr, as well as some cationic proteins encoded by different viruses, share similar physical properties with the unique anti-microbial human cathelicidin LL37 peptide...
April 2018: Medical Hypotheses
Feng Zhao, Xin-Qiang Lan, Yan Du, Pei-Yi Chen, Jiao Zhao, Fang Zhao, Wen-Hui Lee, Yun Zhang
Cationic antimicrobial peptides (AMPs) are considered as important candidate therapeutic agents, which exert potent microbicidal properties against bacteria, fungi and some viruses. Based on our previous findings king cobra cathelicidin (OH-CATH) is a 34-amino acid peptide that exerts strong antibacterial and weak hemolytic activity. The aim of this research is to evaluate the efficacy of both OH-CATH30 and its analog D-OH-CATH30 against clinical isolates comparing with routinely utilized antibiotics in vitro...
March 18, 2018: Zoological Research
Naveen Gupta, Roland Liu, Stephanie Shin, Ranjeet Sinha, Joseph Pogliano, Kit Pogliano, John H Griffin, Victor Nizet, Ross Corriden
Objectives: The role of protease-activated receptor 1 (PAR1) in the pathogenesis of pneumonia and sepsis is ambiguous given the existing literature. As PAR1 is classically activated by the coagulation-based protease thrombin and leads to vascular leakage, our hypothesis was that PAR1 blockade with SCH79797 would be therapeutically beneficial in an experimental model of murine Gram-negative pneumonia. Methods: In this study, we administered SCH79797 via the intrapulmonary route 6 h after the establishment of Escherichia coli pneumonia and observed a significant improvement in survival, lung injury, bacterial clearance and inflammation...
March 5, 2018: Journal of Antimicrobial Chemotherapy
Toshiya Takahashi, Nikhil Nitin Kulkarni, Ernest Y Lee, Ling-Juan Zhang, Gerard C L Wong, Richard L Gallo
Under homeostatic conditions the release of self-RNA from dying cells does not promote inflammation. However, following injury or inflammatory skin diseases such as psoriasis and rosacea, expression of the cathelicidin antimicrobial peptide LL37 breaks tolerance to self-nucleic acids and triggers inflammation. Here we report that LL37 enables keratinocytes and macrophages to recognize self-non-coding U1 RNA by facilitating binding to cell surface scavenger receptors that enable recognition by nucleic acid pattern recognition receptors within the cell...
March 5, 2018: Scientific Reports
Christine S Ahn, William W Huang
Rosacea is a chronic inflammatory skin disorder that is not fully understood but involves the complex interplay of genetic factors, immune dysregulation, neurovascular dysregulation, presence of microorganisms, and environmental factors. Increased activation of the immune system occurs through multiple stimuli, including increased levels of cathelicidin and kallikrein 5, Toll-like receptor 2, matrix metalloproteinases, and mast cells within the skin. Their effects are enhanced by the presence of microorganisms and external triggers, such as UV radiation...
April 2018: Dermatologic Clinics
Andrea Olmos-Ortiz, Janice García-Quiroz, Euclides Avila, Felipe Caldiño-Soto, Ali Halhali, Fernando Larrea, Lorenza Díaz
PROBLEM: Calcitriol, the hormonal form of vitamin D3 (VD), stimulates placental antimicrobial peptides expression; nonetheless, the regulation of calcitriol biosynthesis in the presence of bacterial products and its consequence on placental innate immunity have scarcely been addressed. METHOD OF STUDY: We investigated how some bacterial products modify placental VD metabolism and its ability to induce antimicrobial peptides gene expression. RESULTS: Cultured human trophoblasts biosynthesized calcitriol only in the presence of its precursor calcidiol, a process that was inhibited by cyclic-AMP but stimulated by lipopolysaccharide (LPS)...
March 1, 2018: American Journal of Reproductive Immunology: AJRI
Natalia Becerra, Claudia Marcela Arenas Gómez, Maria Isabel Patiño, Jean Paul Delgado, Carlos Enrique Muskus, Luz Marina Restrepo
Non-viral transfection has important implications on gene therapy, because of its safety. In particular, polyfection and nucleofection are two widely used systems for non-viral gene delivery. Their potential depends on the transfection efficiency achieved, which is influenced in turn by the type of cells transfected and by the plasmid which carries the gene of interest. The efficiency of transfection by polyfection or nucleofection in human fibroblast and keratinocytes was evaluated in this study. Transfections were performed with plasmids containing a gene of interest (Human Cathelicidin Antimicrobial Peptide) and two reporter genes (Red or Green Fluorescent Protein) that included or not an Internal Ribosome Entry Site (IRES)...
February 28, 2018: Tissue Engineering. Part C, Methods
Jim Bartley, Jeff Garrett, Carlos A Camargo, Robert Scragg, Alain Vandal, Rose Sisk, David Milne, Ray Tai, Gene Jeon, Ray Cursons, Conroy Wong
Vitamin D supplementation prevents acute respiratory infections and, through modulating innate and adaptive immunity, could have a potential role in bronchiectasis management. The primary aims of this pilot study were to assess serum 25-hydroxyvitamin D (25(OH)D) levels in New Zealand adults with bronchiectasis, and their 25(OH)D levels after vitamin D3 supplementation. Adults with bronchiectasis received an initial 2.5 mg vitamin D3 oral loading dose and 0.625 mg vitamin D3 weekly for 24 weeks. The primary outcome was serum 25(OH)D levels before and after vitamin D3 supplementation...
January 1, 2018: Chronic Respiratory Disease
Caren C Grabulosa, Silvia R Manfredi, Maria E Canziani, Beata M R Quinto, Rodrigo B Barbosa, Jacqueline F Rebello, Marcelo C Batista, Miguel Cendoroglo, Maria A Dalboni
TLR expression in neutrophils and monocytes is associated with increased cytokine synthesis, resulting in increased inflammation. However, the inflammatory pathway related to TLR and cathelicidin expression in these cells from CKD patients is unclear. To evaluate TLR4, cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 expression in neutrophils and monocytes from HD and CKD patients. Blood samples were drawn from 47 CKD and 43 HD patients and 71 age and gender-matched healthy volunteers (CONT). TLR4 was analyzed using flow cytometry...
February 23, 2018: Experimental Cell Research
Morgan Young-Speirs, Dominique Drouin, Paloma Araujo Cavalcante, Herman W Barkema, Eduardo R Cobo
Cathelicidins are a primitive class of host defense peptides, known for their broad-spectrum antimicrobial activity against bacteria, fungi, and enveloped viruses. However, these small, cationic, proteolytically activated peptides are diverse in structure, encompassing a wide range of activities on host immune and inflammatory cell responses. The dual capacity of cathelicidins to directly control infection and regulate host defenses highlights the potential use of cathelicidins as alternatives to antibiotics and immunomodulators...
February 21, 2018: International Journal of Antimicrobial Agents
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
Yueli Bao, Shanrong Wang, Hongli Li, Yunjiao Wang, Haiyun Chen, Minglong Yuan
BF-30 is a single chain polypeptide of an N-segment with an α-helix from cathelicidin gene encoding, and it contains 30 amino acid residues, with a relative molecular mass and isoelectric point of 3637.54 and 11.79, respectively. Cathelicidin-BF-30 was entrapped in four-arm star-shaped poly(ethylene glycol-b-dl-lactic acid-co-glycolic acid) block copolymers (4-arm-PEG-PLGA) by a double-emulsion solvent-evaporation method. Three release phases of cathelicidin-BF-30loaded 4-arm-PEG-PLGA microspheres were observed, including an initial burst-release phase, followed by a lag phase with minimal drug release and finally a secondary zero-order release phase...
February 23, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Shasha Cai, Xue Qiao, Lan Feng, Nannan Shi, Hui Wang, Huaixin Yang, Zhilai Guo, Mengke Wang, Yan Chen, Yipeng Wang, Haining Yu
Multidrug-resistant Staphylococcus aureus, including MRSA (Methicillin-Resistant) and VRSA (Vancomycin-resistant), causes serious healthcare-associated infections, even sepsis and death. Here, we identified six novel cathelicidins (CATHPb1-6) from Python bivittatu, and CATHPb1 displayed the best in vitro pharmacological and toxicological profile. We further show that CATHPb1 exhibited evident protection in mice MRSA/VRSA infection models, either given 24h before or 4h after infection. The protection was all effective through different administration routes, but was blocked by in vivo depletion of monocyte/macrophages or neutrophils...
February 21, 2018: Journal of Medicinal Chemistry
Rui Yang, Enzhuo Yang, Ling Shen, Robert L Modlin, Hongbo Shen, Zheng W Chen
The ability of Mycobacterium tuberculosis to block host antimicrobial responses in infected cells provides a key mechanism for disease pathogenesis. The immune system has evolved to overcome this blockade to restrict the infection, but it is not clear whether two key innate cytokines (IL-12/IL-18) involved in host defense can enhance antimycobacterial mechanisms. In this study, we demonstrated that the combination of IL-12 and IL-18 triggered an antimicrobial response against mycobacteria in infected macrophages (THP-1 and human primary monocyte-derived macrophages) and pulmonary epithelial A549 cells...
February 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Ernest Y Lee, Michelle W Lee, Gerard C L Wong
Antimicrobial peptides (AMPs) are typically thought of as molecular hole punchers that directly kill pathogens by membrane permeation. However, recent work has shown that AMPs are pleiotropic, multifunctional molecules that can strongly modulate immune responses. In this review, we provide a historical overview of the immunomodulatory properties of natural and synthetic antimicrobial peptides, with a special focus on human cathelicidin and defensins. We also summarize the various mechanisms of AMP immune modulation and outline key structural rules underlying the recently-discovered phenomenon of AMP-mediated Toll-like receptor (TLR) signaling...
February 9, 2018: Seminars in Cell & Developmental Biology
Minhui Dai, Pinhua Pan, Haitao Li, Shuai Liu, Lemeng Zhang, Chao Song, Yi Li, Qian Li, Zhi Mao, Yuan Long, Xiaoli Su, Chengping Hu
Acinetobacter baumannii is a Gram-negative coccobacillus found primarily in hospital settings that has recently emerged as a source of hospital-acquired infections, including bacterial pneumonia. The hLF(1-11) peptide comprising the first 11 N-terminal residues of human lactoferrin exerts antimicrobial activity in vivo and was highly effective against multidrug-resistant A. baumannii strains in vitro and in vivo. Pyroptosis is a caspase-1-dependent inflammatory cell death process and is induced by various microbial infections...
February 1, 2018: Experimental Cell Research
M Elhamouly, T Terada, T Nii, N Isobe, Y Yoshimura
Infectious bronchitis virus (IBV) is an enveloped RNA virus that causes deformities in eggshells. The aim of this study was to investigate the innate immune response to IBV, and to determine whether prostaglandin (PG) E2, which is synthesized during inflammation, is involved in the innate immune response in the uterine mucosa. The effects of intra-oviductal inoculation with attenuated IBV (aIBV) on the expression of viral RNA recognition receptors and innate antiviral factors were examined by real-time PCR and immunohistochemistry, and on PGE2 levels by ELISA...
January 11, 2018: Theriogenology
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
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