Journal Of Investigative Dermatology

Subscribe to Journal Of Investigative Dermatology feed
Journal of Investigative Dermatology RSS feed.
Updated: 1 hour 14 min ago

390 Lipid profiles of facial sebum in Acne Juvenilis in Nigeria

Sun, 2019-09-01 00:00
Acne is a common skin disease among adolescents. Increased sebum output and different distribution of the sebum lipids are implicated in the pathogenesis of acne. Our objective was to obtain biochemical signatures of sebum in acne juvenilis. A cross-sectional analytical study was conducted among adolescents/young adults in Nigeria. Thirty participants with acne (15F, 15M) and 30 age- and sex-matched controls were recruited. Facial sebum was collected from the foreheads and the cheeks with adhesive patches and analysed by HPTLC and GC-MS.

389 Spectrum of actions of PPARγ modulation in acne sebum

Sun, 2019-09-01 00:00
Acne is a chronic inflammatory disease associated with dysseborrhea, hyperkeratinisation, and activation of inflammatory responses in the pilosebaceous unit. A topical gel formulation containing 1% w/w of a newly developed drug having a specific PPARγ-modulating activity has been tested in a phase I trial in 21 patients (10 F, 11 M, age 20.4 ± 5.17 years) with acne grade 3 or 4, as determined by lesion counting. Together with clinical evaluations, both sebum lipidomics and markers of PPARγ-activation were assessed in the sebum sampled from the foreheads with adhesive patches at the baseline and following 3 and 12 weeks of treatment.

388 Treatment with spesolimab, an anti-interleukin-36 receptor antibody, in patients with generalized pustular psoriasis, is associated with the downregulation of biomarkers linked to innate, Th1/17 and neutrophilic pathways

Sun, 2019-09-01 00:00
Generalized pustular psoriasis (GPP) is a rare, life-threatening disease, characterised by recurrent flares of pustular, erythematous rashes, with a strong genetic linkage to the IL-36 pathway. The efficacy and safety of a single, open-label, intravenous dose of spesolimab (BI 655130; 10 mg/kg), an anti-IL-36R monoclonal antibody, was assessed in a Phase I trial (NCT02978690) in 7 patients presenting with a moderate-to-severe GPP flare. To characterise the molecular response to spesolimab, biomarkers in lesional skin and blood were analysed.

387 Ex Vivo Visualization and Extended Drug Release from a Dissolvable Microarray

Sun, 2019-09-01 00:00
The aim of the study was to investigate a dissolvable microarray (MA) patch in terms of skin insertion and drug release in ex vivo human skin for 6 days and in vivo using minipigs for 4 days. The patches contain polymeric, microscopic arrays composed of a fast dissolving drug-free backing layer and slowly dissolving drug containing tips. The calcipotriol and betamethasone dipropionate (BDP) is encapsulated in the tip and delivered in a pain-free and minimally invasive manner by micro-perforation of the stratum corneum with 500 μm long microneedles.

386 Senescence induces pro-apoptotic features in tumor cells enabling targeted senolysis by type I immune-mediators and subsequent phagocytic clearance

Sun, 2019-09-01 00:00
The induction of senescence in cancer cells is an increasingly relevant strategy in tumor therapy. Senescence can be induced using therapeutic compounds (TIS – therapy induced senescence) or type I cytokines IFNy and TNF (CIS – cytokine induced senescence). In vivo treatment with IFNy and TNF can induce senescence in tumors cells. Here we show that CIS induction leads to both pro-apoptotic and anti-apoptotic features in murine cancer cells. Following CIS the majority of cancer cells remains viable, shows SA-ß-Gal activity and arrests proliferation.

385 Ruxolitinib cream ameliorates a preclinical model of skin dermatitis via modulation of inflammatory T-cell subsets

Sun, 2019-09-01 00:00
Allergic contact dermatitis, is driven by an overreaction of the body’s immune system to a normally harmless substance resulting in skin inflammation. Preclinically, topical administration of the T helper 2 (Th2) hapten fluorescein isothiocyanate (FITC) drives an immunogenic sensitization in mice and recall challenge on the ear triggers a localized inflammatory contact hypersensitivity. Pharmacological inhibition of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway has previously demonstrated efficacy in a Phase 2 clinical trial in patients with atopic dermatitis (AD) (NCT03011892).

384 Mitochondria: novel therapeutic targets in atopic dermatitis?

Sun, 2019-09-01 00:00
Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease with a high prevalence worldwide. AD is a complex disease in which epidermal barrier impairment is considered the pathologic cornerstone. Moreover, there is a consensus that abnormal epidermal barrier function is the driving force in the development of skin inflammation, which, in turn, further weakens the barrier and perpetuates a vicious pathological cycle. Defective epidermal barrier leads to sustained epidermal cell renewal.

383 Distinguishable bacterial and fungal dysbiosis in skin of patients with Atopic Dermatitis or Netherton Syndrome

Sun, 2019-09-01 00:00
Atopic dermatitis (AD) is an inflammatory skin disease, in which epidermal barrier impairment, often owing to FLG null mutations, precedes immune hyper-responsiveness. Ichthyosis vulgaris (IV) is characterized by FLG null mutations and non-inflammatory dry skin. SPINK5 null mutations in Netherton syndrome (NS) lead to erythroderma and atopic manifestations. Thus, AD, IV and NS share clinical, genetic or immunological similarities. We sought to evaluate effects of specific skin disease features i.e.

382 Infection by dermatophytes of reconstructed human epidermis is impaired by PD169316 via inhibition of fungal growth

Sun, 2019-09-01 00:00
Dermatophytosis is a superficial infection of keratinized structures of the host caused by keratinolytic filamentous fungi named dermatophytes. Its prevalence is estimated around 20% in humans and has been increasing for the last decade. Classical antifungal agents are rather effective against dermatophytosis but their systemic administration is confronted with several problems. Systemic treatments are expensive and long-lasting, leading to a poor patient compliancy, are often associated with toxicity, and are challenged by the emergence of drug resistance.

381 Evaluation of pharmacological responses to subcutaneous injection of adalimumab in InflammaSkin®, a full-thickness human ex vivo skin model reproducing key features of psoriatic lesions

Sun, 2019-09-01 00:00
Genoskin recently developed InflammaSkin®, a T cell-driven skin inflammation model for psoriasis based on the activation and differentiation into a Th17/Th1 phenotype of skin resident T cells. This ex vivo human skin model is composed of epidermis and dermis with or without the underlying subcutaneous tissue. In the presence of the adipose tissue, it is designed to support subcutaneous delivery of therapeutic compounds. T-cell activation and differentiation in InflammaSkin® with or without adipose tissue, led to a strong upregulation of the release of IL-17A, IL-22, IL-27 and IFNγ pro-inflammatory cytokines after 3- and 7-days culture, as well as an important loss of tissue integrity and cell viability at the histological level.

380 Innate lymphoid cells (ILCs) in healthy and atopic blood

Sun, 2019-09-01 00:00
To investigate the driving force behind the increase of ILCs in atopic dermatitis (AD) skin, we numerically and phenotypically compared ILC (sub)populations in the blood of AD patients and healthy controls (HC). For this purpose, peripheral blood mononuclear cells (PBMCs) were isolated from clinically active AD patients (n=19) and age-matched (35.5 ± 0.1 years) healthy individuals (n=17), immunostained with a panel of subset-characterising antibodies and analysed with a BD FACS Aria III sorter. Total ILCs were defined as viable CD45+, CD3-, Lin-, CD127+, CD161+ mononuclear cells and expressed as percent of CD45+ cells (mean ± SEM).

379 Characterizing the Role of PLCγ2 in Autoantibody-induced Skin Inflammation

Sun, 2019-09-01 00:00
Phospholipase Cγ2 (PLCγ2) is an important member of immunoreceptor signaling expressed mostly in haemopoietic cells. Gain-of-function mutations of PLCγ2 have been reported in both mice and human cases causing a complex syndrome involving skin manifestations resembling epidermolysis bullosa. Previously we showed that PLCγ2 deficient mice remained protected in an autoimmune dermatitis model induced by the passive transfer of autoantibodies against collagen type VII (anti-C7), which is a key anchoring fibril in the dermal-epidermal junction.

378 Induced psoriasis-like inflammation in an air pouch mouse model

Sun, 2019-09-01 00:00
Human psoriasis is a complex autoimmune skin disease, affecting a significant number of the global population. The initiation pathway comprises the differentiation and infiltration of Th17 cells into the skin and is characterized by the production of IL-17A and IL-17F cytokines. This results in a downstream cascade of events, including an exacerbated inflammatory response. In order to establish a more simplified mechanistic mouse model of psoriasis inflammation, we utilized the 6-day air pouch mouse model and aimed for the induction of a psoriasis-like inflammation by injecting a cocktail of inflammatory triggers into the air pouch cavity.

377 MicroRNA as a disease marker of neutrophilic skin disease

Sun, 2019-09-01 00:00
Neutrophilic skin diseases are a group of disorders characterized by intense dermal infiltration of neutrophils without infection. They include pyoderma gangrenosum, pustular psoriasis, Behçet’s disease and so forth. We reported that granulocyte and monocyte adsorption apheresis (GMA) is a useful treatment modality for such refractory skin diseases. Microarray analysis of microRNAs (miRNAs) was performed using sera of patients with neutrophilic skin diseases before and after GMA. Several miRNAs significantly increased in patients compared to control subjects.

376 Establishment of a novel in vivo mouse model of the IL-17 signaling pathway suitable for explorations of PK/PD relationships

Sun, 2019-09-01 00:00
The IL-17 signaling pathway is a key driver of psoriasis and a validated target for treatment of the disease. The purpose of the present study was to establish a mechanistic in vivo mouse model of IL-17 signaling, suitable for modelling of PK/PD relationships for new psoriasis therapies inhibiting this pathway. To obtain an IL-17 induced response in skin, which is the relevant tissue for psoriasis translations, an intradermal cytokine injection model was selected, with proximal biomarkers of clinical relevance as the primary endpoints.

375 The balance between oxidants and antioxidants in patients with genital warts

Sun, 2019-09-01 00:00
Genital human papilloma virus (HPV) infection is the most common sexually transmitted infection. It may be asymptomatic or manifests as benign or malignant lesions. The pathogenesis of HPV infection is not completely elucidated; in most cases spontaneous viral clearance occurs. In our study we have investigated the effect of HPV infection on the balance between oxidants and antioxidants in patients with genital warts. We have determined the serum levels of soluble receptor for advanced glycation end products (sRAGE), total oxidant status (TAS) and total antioxidant status (TOS) in 15 patients with genital warts and 28 healthy subjects.

374 The role of HCV infection on the redox balance in lichen planus patients

Sun, 2019-09-01 00:00
There are several studies showing the link between lichen planus (LP) and hepatitis C virus (HCV) infection. However, the mechanisms involved are incompletely elucidated. Investigating the implication of oxidative stress could shed some light on LP pathogenesis and its link with HCV infection. We have enrolled 12 LP patients with HCV infection (group A), 12 patients without LP, with HCV infection (group B), 31 LP patients without HCV infection (group C), and 26 healthy subjects (control group - group D).

373 Fibroblasts are potentially the key sensors of epidermis lesion through keratinocyte IL-1 signalling

Sun, 2019-09-01 00:00
Our aim was to revisit the primary sterile epidermis lesion considering the alarmins constitutively expressed in the skin tissue and notably the IL-1 family members (IL-1fm) released by lesional keratinocytes. We profiled human keratinocyte IL1fm both at mRNA and protein level and modelized epidermis lesion using a standardized keratinocyte lysate or recombinant IL-1fm in stimulation assays in a panel of skin resident cells or leukocytes. IL-8 and IL-6 were used as consensus chemokine and pro-inflammatory cytokine read-out, respectively.

372 Inhibition of phosphatidylinositol-3-kinase δ improves tissue destruction in pemphigoid diseases by impairing neutrophil function

Sun, 2019-09-01 00:00
Phosphatidylinositol-3-kinase (PI3K) δ-dependent pathways are essential for immune cell activation. Targeting PI3Kδ has beneficial effect in several preclinical models of inflammatory disorders. PI3Kδ contributes to T and B cell development, survival, and antigen recognition as well as various neutrophil functions. Here, we investigated the effect of INCB050465, a novel PI3Kδ-inhibitor, on disease-driving pathways in the pemphigoid diseases (PD) namely bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA), which are autoantibody (aAb)-induced and neutrophil-dependent.

371 The expression of p19 and EBI3 in epidermal keratinocytes under the stimulation with inflammatory cytokines

Sun, 2019-09-01 00:00
Interleukin (IL)-12 family cytokines comprised of a heterodimer, including IL-12, IL-23, IL-27, and IL-35, play critical roles in multiple immune responses such as psoriasis. A new cytokine IL-39 comprised of IL-23p19 and Epstein-Barr Virus-induced 3 (EBI3), was firstly reported in 2015. The mRNA of IL-23p19 and EBI3 has been detected respectively in keratinocytes stimulated with poly(I:C). In addition, IL-39 has been shown to mediate inflammation and expansion of neutrophils in lupus model mice.

Pages