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Cathelicidin is a pleiotropic host defense peptide secreted by epithelial and immune cells. Whether endogenous cathelicidin is protective against ulcerative colitis, however, is unclear. Here we sought to delineate the role of endogenous murine cathelicidin (mCRAMP) and the therapeutic efficacy of intrarectal administration of mCRAMP-encoding plasmid in ulcerative colitis using dextran sulfate sodium (DSS)-challenged cathelicidin-knockout (Cnlp−/−) mice as a model. Cnlp−/− mice had more severe symptoms and mucosal disruption than the wild-type mice in response to DSS challenge. The tissue levels of interleukin-1β and tumor necrosis factor-α, myeloperoxidase activity and the number of apoptotic cells were increased in the colon of DSS-challenged Cnlp−/− mice. Moreover, mucus secretion and mucin gene expression were impaired in Cnlp−/− mice. All these abnormalities were reversed by the intrarectal administration of mCRAMP or mCRAMP-encoding plasmid. Taken together, endogenous cathelicidin may protect against ulcerative colitis through modulation of inflammation and mucus secretion. [ABSTRACT FROM AUTHOR]

The expression of antimicrobial peptides at epithelial surfaces such as skin, lung, and intestine is thought to provide protection against infection. Cathelicidin antimicrobial peptides are essential for the protection of skin against invasive bacterial infection. To determine if cathelicidins are also present in the oral cavity, we examined the expression of both mRNA and protein in mice and human saliva. The murine cathelicidin (CRAMP) was detected in the adult by reverse-transcription/ polymerase chain-reaction (RT-PCR), and in embryonic, newborn, and adult tissues by in situ hybridization and immunohistochemistry. CRAMP mRNA and protein were localized to the salivary glands, specifically in acinar cells of the submandibular gland and palatine minor glands, as well as in lingual epithelium and palatal mucosa. In man, the human cathelicidin LL-37 was detected in human saliva by Western blotting. These results indicate that cathelicidins are present in the salivary system, in some oral epithelia, and in saliva, contributing to broad-spectrum defense of the oral cavity. [ABSTRACT FROM AUTHOR]

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Background: A transition from a subtyping to a phenotyping approach in rosacea is underway, allowing individual patient management according to presenting features instead of categorization by predefined subtypes. The ROSacea COnsensus (ROSCO) 2017 recommendations further support this transition and align with guidance from other working groups., Objectives: To update and extend previous global ROSCO recommendations in line with the latest research and continue supporting uptake of the phenotype approach in rosacea through clinical tool development., Methods: Nineteen dermatologists and two ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and management. Voting was electronic and blinded., Results: Delphi statements on which the panel achieved consensus of ≥ 75% voting 'Agree' or 'Strongly agree' are presented. The panel recommends discussing disease burden with patients during consultations, using four questions to assist conversations. The primary treatment objective should be achievement of complete clearance, owing to previously established clinical benefits for patients. Cutaneous and ocular features are defined. Treatments have been reassessed in line with recent evidence and the prior treatment algorithm updated. Combination therapy is recommended to benefit patients with multiple features. Ongoing monitoring and dialogue should take place between physician and patients, covering defined factors to maximize outcomes. A prototype clinical tool (Rosacea Tracker) and patient case studies have been developed from consensus statements., Conclusions: The current survey updates previous recommendations as a basis for local guideline development and provides clinical tools to facilitate a phenotype approach in practice and improve rosacea patient management. What's already known about this topic? A transition to a phenotype approach in rosacea is underway and is being recommended by multiple working groups. New research has become available since the previous ROSCO consensus, necessitating an update and extension of recommendations. What does this study add? We offer updated global recommendations for clinical practice that account for recent research, to continue supporting the transition to a phenotype approach in rosacea. We present prototype clinical tools to facilitate use of the phenotype approach in practice and improve management of patients with rosacea., (© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Rosacea diagnosis and classification have evolved since the 2002 National Rosacea Society expert panel subtype approach. Several working groups are now aligned to a more patient-centric phenotype approach, based on an individual's presenting signs and symptoms. However, subtyping is still commonplace across the field and an integrated strategy is required to ensure widespread progression to the phenotype approach., Objectives: To provide practical recommendations that facilitate adoption of a phenotype approach across the rosacea field., Methods: A review of the literature and consolidation of rosacea expert experience., Results: We identify challenges to implementing a phenotype approach in rosacea and offer practical recommendations to overcome them across clinical practice, interventional research, epidemiological research and basic science., Conclusions: These practical recommendations are intended to indicate the next steps in the progression from subtyping to a phenotype approach in rosacea, with the goals of improving our understanding of the disease, facilitating treatment developments and ultimately improving care for patients with rosacea., (© 2018 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Previously, we demonstrated that Propionibacterium acnes, a human skin commensal bacterium, ferments glycerol into short-chain fatty acids, including propionic acid. Propionic acid suppressed the growth of Staphylococcus aureus USA300, a community-acquired methicillin-resistant bacterium, in vitro and in vivo. In this study, it is demonstrated that the anti-USA300 activity of propionic acid persisted after buffering the acid with 4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid. This suggests that the growth suppression of USA300 mainly resulted from the antimicrobial activity of propionic acid per se and not from the acidity of the medium. In addition, proprionic acid significantly reduced the intracellular pH of USA300 and exhibited broad-spectrum antimicrobial activity against Escherichia coli and Candida albicans. P. acnes showed a higher tolerance to propionic acid. Next, an esterified derivative of propionic acid was synthesised. Propionic acid and the esterified derivative were equivalent in their efficacy to suppress the growth of USA300 in vitro. The esterified derivative thus provides an alternative to propionic acid as an antimicrobial agent against S. aureus.

Propionibacterium acnes (P. acnes), a Gram-positive anaerobic bacterium, is a commensal organism in human skin. Like human cells, the bacteria produce porphyrins, which exhibit fluorescence properties and make bacteria visible with a Wood's lamp. In this review, we compare the porphyrin biosynthesis in humans and P. acnes. Also, since P. acnes living on the surface of skin receive the same radiation exposure as humans, we envision that the changes in porphyrin profiles (the absorption spectra and/or metabolism) of P. acnes by radiation may mirror the response of human cells to radiation. The porphyrin profiles of P. acnes may be a more accurate reflection of radiation risk to the patient than other biodosimeters/biomarkers such as gene up-/down-regulation, which may be non-specific due to patient related factors such as autoimmune diseases. Lastly, we discuss the challenges and possible solutions for using the P. acnes response to predict the radiation risk.

In mammals, several gene families encode peptides with antibacterial activity, such as the beta-defensins and cathelicidins. These peptides are expressed on epithelial surfaces and in neutrophils, and have been proposed to provide a first line of defence against infection by acting as 'natural antibiotics'. The protective effect of antimicrobial peptides is brought into question by observations that several of these peptides are easily inactivated and have diverse cellular effects that are distinct from antimicrobial activity demonstrated in vitro. To investigate the function of a specific antimicrobial peptide in a mouse model of cutaneous infection, we applied a combined mammalian and bacterial genetic approach to the cathelicidin antimicrobial gene family. The mature human (LL-37) and mouse (CRAMP) peptides are encoded by similar genes (CAMP and Cnlp, respectively), and have similar alpha-helical structures, spectra of antimicrobial activity and tissue distribution. Here we show that cathelicidins are an important native component of innate host defence in mice and provide protection against necrotic skin infection caused by Group A Streptococcus (GAS).

Cathelicidins are a family of peptides thought to provide an innate defensive barrier against a variety of potential microbial pathogens. The human and mouse cathelicidins (LL-37 and CRAMP, respectively) are expressed at select epithelial interfaces where they have been proposed to kill a number of gram-negative and gram-positive bacteria. To determine if these peptides play a part in the protection of skin against wound infections, the anti-microbial activity of LL-37 and CRAMP was determined against the common wound pathogen group A Streptococcus, and their expression was examined after cutaneous injury. We observed a large increase in the expression of cathelicidins in human and murine skin after sterile incision, or in mouse following infection by group A Streptococcus. The appearance of cathelicidins in skin was due to both synthesis within epidermal keratinocytes and deposition from granulocyctes that migrate to the site of injury. Synthesis and deposition in the wound was accompanied by processing from the inactive prostorage form to the mature C-terminal peptide. Analysis of anti-microbial activity of this C-terminal peptide against group A Streptococcus revealed that both LL-37 and CRAMP potently inhibited bacterial growth. Action against group A Streptococcus occurred in conditions that typically abolish the activity of anti-microbial peptides against other organisms. Thus, cathelicidins are well suited to provide defense against infections due to group A Streptococcus, and represent an important element of cutaneous innate immunity.