ECRG4 mediates host response to cutaneous infection by regulating neutrophil recruitment and adhesion receptor expression.

Rapid neutrophil recruitment is critical for controlling infection, with dysfunctional neutrophil responses in diseases like diabetes associated with greater morbidity and mortality. We have shown that the leukocyte protein ECRG4 enhances early neutrophil recruitment to cutaneous wounds and hypothesized that ECRG4 regulates the early host response to infection. Using a cutaneous infection model, we found that ECRG4 KO mice had decreased early neutrophil recruitment with persistent larger lesions, increased bacterial proliferation and systemic dissemination.

Serpin-loaded extracellular vesicles promote tissue repair in a mouse model of impaired wound healing.

Chronic metabolic diseases such as diabetes are characterized by delayed wound healing and a dysregulation of the inflammatory phase of wound repair. Our study focuses on changes in the payload of extracellular vesicles (EVs) communicating between immune cells and stromal cells in the wound bed, which regulate the rate of wound closure. Adoptive transfer of EVs from genetically defined mouse models are used here to demonstrate a functional and molecular basis for differences in the pro-reparative biological activity of diabetic (db/db) vs.

ECRG4 regulates neutrophil recruitment and CD44 expression during the inflammatory response to injury.

The complex molecular microenvironment of the wound bed regulates the duration and degree of inflammation in the wound repair process, while its dysregulation leads to impaired healing. Understanding factors controlling this response provides therapeutic targets for inflammatory disease. Esophageal cancer-related gene 4 (ECRG4) is a candidate chemokine that is highly expressed on leukocytes.

TBC1D3 regulates the payload and biological activity of extracellular vesicles that mediate tissue repair.

Healthy repair of cutaneous injury is a coordinated response of inflammatory cells, secreted factors, and biologically active extracellular vesicles (EVs). Although constitutive release of EVs into biologic fluids is a hallmark of cultured cells and tumors, their payload and biologic activity appears to be tightly regulated. We show that Tre-2/Bub2/Cdc16 (TBC1) domain family member 3 (TBC1D3) drives the release of an EV population that causes a decrease in phosphorylation of the transcription factor signal transducer and activator of transcription 3 in naive recipient cells.

Continuity of care in dermatology residency programs in the United States.

Purpose: As established by the AccreditationCouncil for Graduate Medical Education (ACGME),dermatology residents in the United States must participate in continuity clinic. This requirement may be achieved through multiple means, allowing for program variation. To better assess continuity clinic's role in resident learning, more data on this component of graduate medical education is needed.

Activation of Parathyroid Hormone 2 Receptor Induces Decorin Expression and Promotes Wound Repair.

In this study, we report that TIP39, a parathyroid hormone ligand family member that was recently identified to be expressed in the skin, can induce decorin expression and enhance wound repair. Topical treatment of mice with TIP39 accelerated wound repair, whereas TIP39-deficient mice had delayed repair that was associated with formation of abnormal collagen bundles. To study the potential mechanism responsible for the action of TIP39 in the dermis, fibroblasts were cultured in three-dimensional collagen gels, a process that results in enhanced decorin expression unless activated to differentiate to adipocytes, whereupon these cells reduce expression of several proteoglycans, including decorin.

Selective antimicrobial action is provided by phenol-soluble modulins derived from Staphylococcus epidermidis, a normal resident of the skin.

Antimicrobial peptides serve as a first line of innate immune defense against invading organisms such as bacteria and viruses. In this study, we hypothesized that peptides produced by a normal microbial resident of human skin, Staphylococcus epidermidis, might also act as an antimicrobial shield and contribute to normal defense at the epidermal interface. We show by circular dichroism and tryptophan spectroscopy that phenol-soluble modulins (PSMs) gamma and delta produced by S.

Mast cell cathelicidin antimicrobial peptide prevents invasive group A Streptococcus infection of the skin.

Mast cells (MC) express cathelicidin antimicrobial peptides that act as broad-spectrum antibiotics and influence the immune defense of multiple epithelial surfaces. We hypothesized that MC help protect against skin infection through the expression of cathelicidin. The susceptibility of MC-deficient mice (Kit Wsh(-/-)) to invasive group A streptococcus (GAS) was compared with control mice.

Expression of antimicrobial peptides in the normal and involved skin of patients with infective cellulitis.

Background: Endogenous antimicrobial peptides participate in the innate defense of skin against a variety of pathogens. The systemic expression of these peptides in normal-appearing skin of patients with infective cellulitis is unknown.

Methods: Study patients were adults with infective cellulitis and signs of systemic inflammation.

Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea.

Acne rosacea is an inflammatory skin disease that affects 3% of the US population over 30 years of age and is characterized by erythema, papulopustules and telangiectasia. The etiology of this disorder is unknown, although symptoms are exacerbated by factors that trigger innate immune responses, such as the release of cathelicidin antimicrobial peptides. Here we show that individuals with rosacea express abnormally high levels of cathelicidin in their facial skin and that the proteolytically processed forms of cathelicidin peptides found in rosacea are different from those present in normal individuals.

Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism.

An essential element of the innate immune response to injury is the capacity to recognize microbial invasion and stimulate production of antimicrobial peptides. We investigated how this process is controlled in the epidermis. Keratinocytes surrounding a wound increased expression of the genes coding for the microbial pattern recognition receptors CD14 and TLR2, complementing an increase in cathelicidin antimicrobial peptide expression.

Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin.

The presence of cathelicidin antimicrobial peptides provides an important mechanism for prevention of infection against a wide variety of microbial pathogens. The activity of cathelicidin is controlled by enzymatic processing of the proform (hCAP18 in humans) to a mature peptide (LL-37 in human neutrophils). In this study, elements important to the processing of cathelicidin in the skin were examined.

Control of the innate epithelial antimicrobial response is cell-type specific and dependent on relevant microenvironmental stimuli.

Immune defence against microbes depends in part on the production of antimicrobial peptides, a process that occurs in a variety of cell types but is incompletely understood. In this study, the mechanisms responsible for the induction of cathelicidin and beta-defensin antimicrobial peptides were found to be independent and specific to the cell type and stimulus. Vitamin D3 induced cathelicidin expression in keratinocytes and monocytes but not in colonic epithelial cells.

The mammalian ionic environment dictates microbial susceptibility to antimicrobial defense peptides.

Antimicrobial peptides (AMPs) have been shown in animal and human systems to be effective natural antibiotics. However, it is unclear how they convey protection; they often appear inactive when assayed under culture conditions applied to synthetic antibiotics. This inactivation has been associated with loss of function in physiological concentrations of NaCl or serum.

Structure-function relationships among human cathelicidin peptides: dissociation of antimicrobial properties from host immunostimulatory activities.

Cathelicidins and other antimicrobial peptides are deployed at epithelial surfaces to defend against infection. These molecules have broad-spectrum killing activity against microbes and can have effects on specific mammalian cell types, potentially stimulating additional immune defense through direct chemotactic activity or induction of cytokine release. In humans, the cathelicidin hCAP18/LL-37 is processed to LL-37 in neutrophils, but on skin it can be further proteolytically processed to shorter forms.

Expression and secretion of cathelicidin antimicrobial peptides in murine mammary glands and human milk.

Mammalian milk possesses inherent antimicrobial properties that have been attributed to several diverse molecules. Recently, antimicrobial peptides that belong to the cathelicidin gene family have been found to be important to the mammalian immune response. This antimicrobial is expressed in several tissues and increased in neonatal skin, possibly to compensate for an immature adaptive immune response.

Innate immune defense of the nail unit by antimicrobial peptides.

Background: The nail is susceptible to microbial invasion, yet is usually able to defend itself from infection. This occurs despite isolation from cell-mediated immunity.

Objective: The aim of this study was to determine whether soluble innate immune molecules are present in the nail environment that can protect against microbial colonization.

Postsecretory processing generates multiple cathelicidins for enhanced topical antimicrobial defense.

The production of antimicrobial peptides and proteins is essential for defense against infection. Many of the known human antimicrobial peptides are multifunctional, with stimulatory activities such as chemotaxis while simultaneously acting as natural antibiotics. In humans, eccrine appendages express DCD and CAMP, genes encoding proteins processed into the antimicrobial peptides dermcidin and LL-37.

Neonatal skin in mice and humans expresses increased levels of antimicrobial peptides: innate immunity during development of the adaptive response.

The expression of antimicrobial peptides and proteins is an important innate immune defense mechanism that has recently been shown to be essential for cutaneous defense against invasive bacterial disease. Newborns have an immature cellular immune defense system that leads to increased susceptibility to infections. Here we show that skin from embryonic and newborn mice, as well as human newborn foreskin, express antimicrobial peptides of the cathelicidin and beta-defensin gene families.

Cathelicidin anti-microbial peptide expression in sweat, an innate defense system for the skin.

The eccrine gland is one of the major cutaneous appendages and secretes sweat. Its principal function is thermoregulation during exposure to a hot environment or physical exercise. In addition to this function, we show that LL-37, a member of cathelicidin family of anti-microbial peptides, is expressed in sweat.