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Cathelicidins comprise a family of antimicrobial peptides sharing a highly conserved cathelin domain. Here we report that the entire chicken genome encodes three cathelicidins, namely fowlicidin-1 to -3, which are densely clustered within a 7.5-kb distance at the proximal end of chromosome 2p. Each fowlicidin gene adopts a fourexon, three-intron structure, typical for a mammalian cathelicidin. Phylogenetic analysis revealed that fowlicidins and a group of distantly related mammalian cathelicidins known as neutrophilic granule proteins are likely to originate from a common ancestral gene prior to the separation of birds from mammals, whereas other classic mammalian cathelicidins may have been duplicated from the primordial gene for neutrophilic granule proteins after mammals and birds are diverged. Similar to ovine cathelicidin SMAP-29, putatively mature fowlicidins displayed potent and salt-independent activities against a range of Gram-negative and Gram-positive bacteria, including antibiotic-resistant strains, with minimum inhibitory concentrations in the range of 0.4-2.0 microm for most strains. Fowlicidin-1 and -2 also showed cytotoxicity, with 50% killing of mammalian erythrocytes or epithelial cells in the range of 6-40 microm. In addition, two fowlicidins demonstrated a strong positive cooperativity in binding lipopolysaccharide (LPS), resulting in nearly complete blockage of LPS-mediated proinflammatory gene expression in RAW264.7 cells. Taken together, fowlicidin-1 and -2 are clearly among the most potent cathelicidins that have been reported. Their broad spectrum and salt-insensitive antibacterial activities, coupled with their potent LPS-neutralizing activity, make fowlicidins excellent candidates for novel antimicrobial and anti-sepsis agents.
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http://dx.doi.org/10.1074/jbc.M507180200 | DOI Listing |
Front Cell Infect Microbiol
December 2024
Servicio de Microbiología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
Introduction: Murepavadin is an antimicrobial peptide (AMP) in clinical development that selectively targets LptD and whose resistance profile remains unknown. We aimed to explore genomic modifications and consequences underlying murepavadin and/or colistin susceptibility.
Methods: To define genomic mechanisms underlying resistance, we performed two approaches: 1) a genome-wide association study (GWAS) in a clinical collection (n=496), considering >0.
Stem Cell Res Ther
December 2024
Key Lab. of Oral Diseases Research, College and Hospital of Stomatology, Anhui Medical University, Hefei, 230032, Anhui Province, China.
Background: Inflammation often causes irreversible damage to dental pulp tissue. Dental pulp stem cells (DPSCs), which have multidirectional differentiation ability, play critical roles in the repair and regeneration of pulp tissue. However, the presence of proinflammatory factors can affect DPSCs proliferation, differentiation, migration, and other functions.
View Article and Find Full Text PDFImmun Inflamm Dis
December 2024
Department of Dermatology, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha, China.
Background: Rosacea is a common inflammatory skin disorder characterized by frequent facial flushing, erythema, telangiectasia, and papules, with a higher incidence observed in individuals aged 30-50 years and a tendency to decrease in the elderly. This age-related decline in incidence drew our attention to further explore the relationship between rosacea pathogenesis and aging.
Methods: We analyzed the incidence of rosacea across 8340 individuals without systemic diseases.
Int J Mol Sci
November 2024
Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing 400715, China.
Cathelicidins have anti-inflammatory activity and chicken cathelicidin-2 (CATH-2) has shown to modulate immune response, but the underlying mechanism of its anti-inflammation is still unclear. Therefore, in this study, we investigated the anti-inflammatory activity of CATH-2 on murine peritoneal macrophages during avian pathogenic (APEC) infection. The results showed that CATH-2 priming significantly reduced the production of IL-1β, IL-6, IL-1α, and IL-12.
View Article and Find Full Text PDFPharmacol Res
December 2024
Department of Urology, Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address:
Heart disease is a common human disease with high morbidity and mortality. Timely and effective prevention and treatment is an urgent clinical problem. The pathogenesis of heart disease is complex and diverse, involving hypertension, diabetes, atherosclerosis, drug toxicity, thrombosis, infection and other aspects.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!