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Nishanth Makthal, Hackwon Do, Arica R VanderWal, Randall J Olsen, James M Musser, Muthiah Kumaraswami
Bacterial virulence factor production is a highly coordinated process. The temporal pattern of bacterial gene expression varies in different host anatomic sites to overcome niche-specific challenges. The human pathogen group A streptococcus (GAS) produces a potent secreted protease, SpeB, that is crucial for pathogenesis. Recently, we discovered that a quorum-sensing pathway comprised of a leaderless short peptide, SpeB-inducing peptide (SIP), and cytosolic global regulator, RopB, controls speB expression in concert with bacterial population density...
March 12, 2018: Infection and Immunity
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
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
Akshay Bareja, Shubham Patel, Conrad P Hodgkinson, Alan Payne, Victor J Dzau
The development of biased agonist drugs is widely recognized to be important for the treatment of many diseases, including cardiovascular disease. While GPCR biased agonism has been heavily characterized there is a distinct lack of information with respect to RTK biased agonism both in the identification of biased agonists as well as their attendant mechanisms. One such RTK, the Insulin-like Growth Factor 1 Receptor (IGF1R) plays an important role in a range of biological and disease processes. The micropeptide LL37 has been described as a biased agonist of the IGF1R...
February 27, 2018: Cellular Signalling
Robert Szulcek, Christian Bollensdorff, Peter Hordijk, Matthias Gabriel
The chemical coupling of growth factors to solid substrates are discussed as an alternative to delivery systems. Utilizing entire proteins for this application is hampered by safety and stability considerations. Instead, growth factor mimicking peptides are of great interest for biomedical applications, such as tissue engineering, due to their purity and stability. The human cathelicidin derived antimicrobial peptide LL37, beside its microbicidal activity, was shown to stimulate endothelial cell growth when used in a soluble form...
January 20, 2018: Biochemical and Biophysical Research Communications
N Dong, X R Li, X Y Xu, Y F Lv, Z Y Li, A S Shan, J L Wang
Facing rising global antibiotics resistance, physical membrane-damaging antimicrobial peptides (AMPs) represent promising antimicrobial agents. Various strategies to design effective hybrid peptides offer many advantages in overcoming the adverse effects of natural AMPs. In this study, hybrid peptides from different species were investigated, and three hybrid antimicrobial peptides, LI, LN, and LC, were designed by combining the typical fragment of human cathelicidin-derived LL37 with either indolicidin, pig nematode cecropin P1 (CP-1) or rat neutrophil peptide-1 (NP-1)...
December 27, 2017: Amino Acids
Yongwei Li, Zhengfei Shan, Bin Yang, Diandong Yang, Changping Men, Yuanshan Cui, Jitao Wu
Ureter reconstruction is a difficult procedure in urology. Adipose-derived stem cells (ADSCs), along with multipotency and self-renewal capacity, are a preferred choice for tissue engineering-based ureteral reconstruction. We explored the synergic role of cathelicidin LL37 (LL37) in epithelial and smooth-muscle-like differentiation. ADSCs were separated from adipose tissues of mouse and characterized by flow cytometry. The ADSCs were then stably transfected with pGC-FU-GFP (pGC) or pGC containing full-length LL37 (pGC-LL37), respectively...
November 2017: Biochemistry. Biokhimii︠a︡
VijayKumar Patra, Gerlinde Mayer, Alexandra Gruber-Wackernagel, Michael Horn, Serena Lembo, Peter Wolf
BACKGROUND: Polymorphic light eruption (PLE) has been attributed to type IV, most likely delayed-type hypersensitivity response (adaptive immunity) but little is known on innate immunity, especially antimicrobial peptides (AMPs) in the disease. Abnormalities in AMP expression have been linked to pathological skin conditions such as atopic dermatitis (AD) and psoriasis. METHODS: AMP profiling was done in PLE skin samples (n,12) compared with that of healthy (n,13), atopic (n,6) and psoriatic skin (n,6)...
October 16, 2017: Photodermatology, Photoimmunology & Photomedicine
Ernest Y Lee, Toshiya Takahashi, Tine Curk, Jure Dobnikar, Richard L Gallo, Gerard C L Wong
Double-stranded RNA (dsRNA) induces production of pro-inflammatory cytokines in normal human epidermal keratinocytes (NHEK) by specific binding to endosomal Toll-like receptor-3 (TLR3). Recently, it has been shown that hyperactivation of TLR3 in psoriatic keratinocytes by dsRNA can occur in the presence of human antimicrobial peptide (AMP) LL37. Here, we combine synchrotron X-ray scattering, microscopy, computer simulations, and measurements of NHEK cytokine production to elucidate a previously unanticipated form of specific molecular pattern recognition...
October 19, 2017: ACS Nano
Zunpeng Liu, Xue Yuan, Min Liu, Gabriela Fernandes, Yejia Zhang, Shuting Yang, Ciprian N Ionita, Shuying Yang
Repair and regeneration of inflammation-induced bone loss remains a clinical challenge. LL37, an antimicrobial peptide, plays critical roles in cell migration, cytokine production, apoptosis, and angiogenesis. Migration of stem cells to the affected site and promotion of vascularization are essential for tissue engineering therapy, including bone regeneration. However, it is largely unknown whether LL37 affects mesenchymal stem cell (MSC) behavior and bone morphogenetic protein 2 (BMP2)-mediated bone repair during the bone pathologic remodeling process...
September 14, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
Céline M Desmet, Gaëlle Vandermeulen, Caroline Bouzin, Martin C Lam, Véronique Préat, Philippe Levêque, Bernard Gallez
PURPOSE: To investigate the value of electron paramagnetic resonance oximetry to follow oxygenation in wounds treated by a plasmid-encoding host defense peptide hCAP-18/LL37. METHODS: Flaps were created on diabetic mice (7- or 12-week-old db/db mice) presenting different levels of microangiopathy. The hCAP-18/LL37-encoding plasmids were administered in wounds by electroporation. Low-frequency electron paramagnetic resonance oximetry using lithium phthalocyanine as the oxygen sensor was used to monitor wound oxygenation in flaps during the healing process...
October 5, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Sarah E Wood, Gaurav Sinsinbar, Sushanth Gudlur, Madhavan Nallani, Che-Fan Huang, Bo Liedberg, Milan Mrksich
Identifying peptide substrates that are efficiently cleaved by proteases gives insights into substrate recognition and specificity, guides development of inhibitors, and improves assay sensitivity. Peptide arrays and SAMDI mass spectrometry were used to identify a tetrapeptide substrate exhibiting high activity for the bacterial outer-membrane protease (OmpT). Analysis of protease activity for the preferred residues at the cleavage site (P1, P1') and nearest-neighbor positions (P2, P2') and their positional interdependence revealed FRRV as the optimal peptide with the highest OmpT activity...
September 20, 2017: Angewandte Chemie
Nathella Pavan Kumar, Kadar Moideen, Vijay Viswanathan, Shanmugam Sivakumar, Pradeep A Menon, Hardy Kornfeld, Subash Babu
BACKGROUND: The association of antimicrobial peptides (AMPs) with tuberculosis-diabetes comorbidity (PTB-DM) is not well understood. METHODS: To study the association of AMPs with PTB-DM, we examined the systemic levels of cathelicidin (LL37), human beta defensin- 2 (HBD2), human neutrophil peptides 1-3, (HNP1-3) and granulysin in individuals with either PTB-DM, PTB, latent TB (LTB) or no TB infection (NTB). RESULTS: Circulating levels of cathelicidin and HBD2 were significantly higher and granulysin levels were significantly lower in PTB-DM compared to PTB, LTB or NTB, while the levels of HNP1-3 were significantly higher in PTB-DM compared to LTB or NTB individuals...
2017: PloS One
C Chen, B Deslouches, R C Montelaro, Y P Di
OBJECTIVES: Pseudomonas aeruginosa is a common cause of pneumonia in patients with cystic fibrosis with the property to generate multidrug resistance against clinically used antibiotics. Antimicrobial peptides (AMPs) are a diverse group of effector molecules of the innate immune system that protect the host against pathogens. However, the lack of activity in common biological matrices has hampered efforts towards clinical development. In this study, we evaluated the therapeutic potential of the engineered AMP WLBU2 via direct airway delivery in a murine model of P...
September 4, 2017: Clinical Microbiology and Infection
Yongwei Li, Jitao Wu, Fan Feng, Changping Men, Diandong Yang, Zhenli Gao, Zhe Zhu, Yuanshan Cui, Hongwei Zhao
AIM: We constructed a new artificial, long tubular acellular matrix, seeded with autologous progenitor cells transfected with the sequence to produce the antibiotic peptide LL37 and another two common seeding cells, which might be adopted for patients requiring repair of long segment of the urethra. MATERIALS AND METHODS: Autologous endothelial progenitor cells transfected by lentiviral vectors expressing antibiotic peptide LL37, as well as urothelial and smooth muscle cells from New Zealand white male rabbits, were cultured and seeded onto preconfigured acellular collagen-based tubular matrices (3 cm in length)...
August 2017: Anticancer Research
Michela Comune, Akhilesh Rai, Kiran K Chereddy, Sandra Pinto, Sezin Aday, André F Ferreira, Alessandra Zonari, Josephine Blersch, Rodrigo Cunha, Ricardo Rodrigues, Juan Lerma, Pedro N Simões, Veronique Préat, Lino Ferreira
Chronic skin wounds affect ≈3% of persons aged >60years (Davies et al., 2007) [1]. These wounds are typically difficult to heal by conventional therapies and in many cases they get infected making even harder the regeneration process. The antimicrobial peptide (AMP) LL37 combines antimicrobial with pro-regenerative properties and thus represents a promising topical therapy to address both problems. Here, we investigated the wound healing potential of soluble and immobilized LL37 (LL37-conjugated gold nanoparticles, LL37-Au NPs), both in vitro (migration of keratinocytes) and in vivo (skin wound healing)...
July 8, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
Joanna E Payne, Alice V Dubois, Rebecca J Ingram, Sinead Weldon, Clifford C Taggart, J Stuart Elborn, Michael M Tunney
There is a clear need for new antimicrobials to improve current treatment of chronic lung infection in people with cystic fibrosis (CF). This study determined the activities of antimicrobial peptides (AMPs) and ivacaftor, a novel CF transmembrane conductance regulator potentiator, for CF treatment. Antimicrobial activities of AMPs [LL37, human β-defensins (HβD) 1-4 and SLPI] and ivacaftor against clinical respiratory isolates (Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus spp., Achromobacter spp...
June 27, 2017: International Journal of Antimicrobial Agents
Kun Li, Zhang-Lei Mu, Xue Chen, Guang-Dong Wen, Yan Zhao, Jian-Zhong Zhang
BACKGROUND: Graft-versus-host disease (GVHD) is a common complication of hematopoietic stem cell transplantation. Skin barrier disruption could induce thymic stromal lymphopoietin (TSLP) expression, and the expression of TSLP was increased in lesions of atopic dermatitis (AD)-like GVHD and lichen planus (LP)-like GVHD. This study attempted to investigate the skin barrier function of AD-like GVHD and LP-like GVHD and possible mechanisms. METHODS: Eighteen AD-like GVHD patients, 12 LP-like GVHD patients, and 14 healthy volunteers were enrolled in this study...
June 20, 2017: Chinese Medical Journal
Judilyn Fuentes-Duculan, Kathleen M Bonifacio, Jason E Hawkes, Norma Kunjravia, Inna Cueto, Xuan Li, Juana Gonzalez, Sandra Garcet, James G Krueger
Psoriasis is a common immune-mediated disease that affects 2%-4% of individuals in North America and Europe. In the past decade, advances in research have led to an improved understanding of immune pathways involved in the pathogenesis of psoriasis and has spurred the development of targeted therapeutics. Recently, three psoriasis autoantigens have been described: cathelicidin (LL37), a disintegrin and metalloprotease domain containing thrombospondin type 1 motif-like 5 (ADAMTSL5), and lipid antigens generated by phospholipase A2 (PLA2) group IVD (PLA2G4D)...
November 2017: Experimental Dermatology
Satya Sree Kolar, Hasna Baidouri, Alison M McDermott
Purpose: Fusarium solani (F. solani) keratitis is a potentially sight-threatening fungal infection of the cornea. Antimicrobial peptides (AMPs), such as human β-defensins (hBDs) and cathelicidins, essential components of the immune system, likely have a protective role against F. solani keratitis. We examined the role of pattern recognition receptors (PRRs), Dectin-1, and TLR2 in F. solani-induced modulation of AMP expression in vitro. Methods: Human corneal epithelial cells (HCECs) were exposed to heat-inactivated F...
May 1, 2017: Investigative Ophthalmology & Visual Science
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