Nitric oxide (NO) plays an important role in the cutaneous response to UV radiation and in cutaneous inflammation. The presence of inducible NO synthase protein in a number of inflammatory dermatoses, coupled with the induction of an intense cutaneous inflammatory infiltrate following topical application of the NO donor-acidified nitrite (NO2(-)), ...

Recreational and occupational exposure to seawater (SW), have increased but the effect of SW on skin has not been elucidated. The purpose of present study was to assess the effects of SW immersion on the dorsal skin in hairless mice. Adult hairless mice were individually immersed in SW for 3 ...

Contact dermatitis is a common skin disease caused by contact with irritants or allergens. Irritant contact dermatitis is a result of nonspecific irritant factors, which cause activation of mainly innate immunity, resulting in skin inflammation. Contact hypersensitivity, which manifests itself as allergic contact dermatitis, is result of adaptive immune response, ...

The skin, situated at the critical juncture between the host and the environment, is subject to a variety of potentially damaging agents including microbial organisms, toxins, and gene-altering radiation. Diverse immunocytes, including those resident in the skin and those with the capacity to traffic to and from the skin, direct ...

Atopic dermatitis (AD) is a highly pruritic, chronic, multifactorial skin disease predisposing to bacterial and viral infections based on abnormalities of the innate and acquired immune system. The innate system quickly mobilizes an inflexible, standardized first-line response against different pathogens. Epidermal barrier dysfunction results in increased protein allergen penetration through ...

Psoriasis and psoriatic arthritis (PsA) are common diseases associated with considerable morbidity and disability. Their pathophysiology comprises a dysfunctional stromal-immune cell and cytokine network leading to inflammation of skin, entheses and joints. Recent advances in understanding of disease pathogenesis have led to the introduction of novel therapeutics providing the ultimate ...

Patients with atopic dermatitis (AD) exposed to the vaccinia virus (VV) smallpox vaccine have an increased risk of developing eczema vaccinatum. To investigate the effects of local allergic skin inflammation on vaccinia immunity. BALB/c mice were epicutaneously sensitized with ovalbumin (OVA) to induce allergic skin inflammation or with saline control, ...

Skin is the largest organ of the human body that harbors a robust and versatile immune surveillance system. Whereas impaired immune function of the skin enables tumor growth, excessive immune activation results in different inflammatory diseases of the skin. HLA-G is a non-classical MHC class I molecule that was initially ...

Advances in our understanding of the skin immune system have a major impact on studies of skin autoimmunity, graft-versus-host disease, inflammation, and cancer as well as on the development of novel vaccines and immunotherapy approaches. In this issue of the JCI, Zaba et al. carefully dissected the complex network of ...

Exposing experimental animals or human volunteers to UVA II (320-340 nm) radiation after immunization suppresses immunologic memory and the elicitation of delayed-in-time hypersensitivity reactions. Previous studies indicated that the mechanisms underlying UVA-induced immune suppression are similar to those described for UVB-induced immune suppression, i.e. transferred by T regulatory cells, overcome ...

Disorders of the skin immune activity are implicated in the pathogenesis of acquired inflammatory skin disorders. Inflammatory diseases including psoriasis, atopic dermatitis, lichen planus and vitiligo have also been associated with local alterations of adrenergic mechanisms and emotional stress. Here we show that the beta-adrenergic receptors antagonist propranolol along with ...

Quinacrine (QC) is an anti-inflammatory drug that has been used for the treatment of malaria and rheumatoid diseases. The mechanism(s) underlying the anti-inflammatory activity of QC remains poorly understood. We recently reported the QC-mediated inhibition of the NF-kappaB pathway using an in vitro model. To test this potential mechanism in ...

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 ...

Inflammatory diseases at epithelial borders develop from aberrant interactions between resident cells of the tissue and invading immunocytes. Here, we unraveled basic functions of epithelial cells and immune cells and the sequence of their interactions in an inflammatory skin disease. Ubiquitous deficiency of the IkappaBalpha protein (Ikba(Delta)(/Delta)) as well as ...

Ultraviolet (UV) irradiation causes multiple pathologic changes in the skin including inflammation, immune suppression, photoaging, and cancer. Effects of UV irradiation include the activation of numerous signal transduction pathways, including the mitogen-activated protein kinases (MAPK), and the activation of transcription factors such as nuclear factor kappa B (NFkappaB). These responses ...

OBJECTIVE: Tissue fibrosis is a hallmark compromising feature of many disorders. In this study, we investigated the antifibrogenic effects of the histone deacetylase inhibitor trichostatin A (TSA) on cytokine-driven fibrotic responses in vitro and in vivo. METHODS: Skin fibroblasts from patients with systemic sclerosis (SSc) and normal healthy control subjects ...

The epidermis, like many other tissues, reacts to mechanical stress by increasing cell proliferation. Mechanically stressed skin regions often develop thicker skin and hyperkeratosis. Interestingly, a large number of skin diseases are accompanied by epidermal proliferation and hyperkeratosis even under normal mechanical stress conditions. Although, some of the molecular pathways ...

The epidermis must be protected against excess apoptotic cell death in response to ultraviolet-B (UV-B) irradiation. p53 is known to be critical for this protection. Although the p53 family member DeltaNp51B/DeltaNp63alpha (an N terminal-deleted form of p51/p63) is abundantly expressed in keratinocytes, its contribution to UV-B-dependent apoptosis is largely unknown. ...

It has long been known that human keratinocytes are a potent source of the proinflammatory cytokines proIL-1alpha and -1beta[1], which are activated and released in response to UV irradiation [2]. However, the intracellular pathways, which regulate maturation and secretion of IL-1 in keratinocytes, are unknown. Here we show that the ...

Psoriasis has been considered an autoimmune, T cell-mediated disorder in which adaptive immune responses predominate over those of non-antigen-specific innate immunity. To test this hypothesis, we profiled the transcriptome of psoriatic tissue and compared the data with that from cultured human keratinocytes exposed to the proinflammatory cytokine interleukin (IL)-1alpha and ...

BACKGROUND: Psoriasis is a chronic inflammatory skin disease principally mediated by activated T cells, which release proinflammatory cytokines with reactive epidermal changes in the skin, producing the characteristic lesions of psoriasis. New research into possible treatment options has been inspired by increased understanding of the pathophysiology of psoriasis and advances ...

Advanced therapies combating acute and chronic skin wounds are likely to be brought about using our knowledge of regenerative medicine coupled with appropriately tissue-engineered skin substitutes. At the present time, there are no models of an artificial skin that completely replicate normal uninjured skin. Natural biopolymers such as collagen and ...

The pathogenicity of skin disorders involves a complexity of physiological, immunological, environmental, and genetic phenomena. This review focuses on cross-talks between two main agents, the oxidants and cytokines network, which have recently been found to play important roles in the pathophysiology of a large variety of skin disorders, including carcinogenesis, ...

The proinflammatory capacities of the skin and the presence of high numbers of resident dendritic cells (DCs) constitute an ideal microenvironment for successful immunizations. Regardless of the ability of DCs to respond to local inflammatory signals in an immunostimulatory fashion, the immune functions of skin-resident DCs remain controversial, and epidermal ...

Skin is one of the largest organs of the body, and is formed during development through a highly orchestrated process involving mesenchymal-epithelial interactions, cell commitment, and terminal differentiation. It protects against microorganism invasion and UV irradiation, inhibits water loss, regulates body temperature, and is an important part of the immune ...

In the human body, every day billions of apoptotic cells are produced. Removal of these cells is necessary, to prevent the release of intracellular toxic constituents, and occurs very effectively via phagocytosis by (semi)-professional phagocytes. This elimination process occurs rapidly and without inflammation. In systemic lupus erythematosus (SLE) a disturbed ...

The anti-inflammatory mechanisms of adapalene, a synthetic retinoid used for the treatment of acne patients, are partially understood. They seem particularly related to the modulation of the non-specific immunity. Recent studies have shown that Toll-like receptor (TLR)-2 expression, a receptor of the innate immune system, was increased in acne lesions ...

Animal skin separates the inner world of the body from the largely hostile outside world and is actively involved in the defence against microbes. However, the skin is no perfect defence barrier and many microorganisms have managed to live on or within the skin as harmless passengers or as disease-causing ...

BACKGROUND: Psoriasis is a chronic inflammatory skin disease principally mediated by activated T cells, which release proinflammatory cytokines with reactive epidermal changes in the skin, producing the characteristic lesions of psoriasis. New research into possible treatment options has been inspired by increased understanding of the pathophysiology of psoriasis and advances ...

BACKGROUND: The histopathologic changes characteristic of psoriasis might be related to suppressed apoptosis. The P53 and Bcl-2 proteins play a central role in the regulation of apoptosis. This study aimed to evaluate P53 and Bcl-2 expression and apoptotic cells in the psoriatic skin before and after topical calcipotriol therapy. METHODS: ...

In 1970, Gershon was the first to propose that T cells, in addition to their helper activity, can also play a role as regulatory cells capable of suppressing immune responses. However, the initial strong interest in T cell-mediated suppression was followed by a period of doubt and skepticism. Since the ...

Heme oxygenase 1 (HO-1) is an antiinflammatory stress protein. Its immunosuppressive and cytoprotective activities have been demonstrated in several animal models. The underlying mechanisms, however, are poorly understood. This study demonstrates for the first time that the physiological induction of HO-1 is important for the limitation and resolution of T ...

Early inflammatory changes in psoriatic plaques were investigated immunohistochemically by studying the normal-appearing skin adjacent to the plaques (perilesional skin), lesional skin, and distant uninvolved skin from psoriasis patients. Perilesional epidermis contained numerous CD1a-positive Langerhans cells, some of which expressed HLA-DR, CD83, CD80, and CD86, at the same time expressing ...

BACKGROUND: Skin develops through a process of epidermal proliferation, maturation, and remodelling of the epidermis and dermis. This period also involves the maturation of the skin immune system, such that antigen applied though the skin of a neonatal mouse always results in immunosuppression, whereas in adults, immunity will occur. OBJECTIVES: ...

Psoriasis is a T-cell-mediated chronic inflammatory skin disease believed to be of autoimmune nature that can be triggered or worsened by streptococcal throat infections. In addition to conventional chronic inflammatory changes, psoriasis is characterized by complex and striking alterations in epidermal growth and differentiation. Psoriasis is generally not observed in ...

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with immunopathologic features that vary depending on the duration of the lesion. The lesioned skin of AD patients shows an increased number of inflammatory cells such as eosinophils, mast cells and mononuclear cells in the dermis and superficial Staphylococcus aureus ...

UVB irradiation modulates immune responses in the skin and is a major cause of sunburn, during which neutrophils accumulate in the skin. Because of their abundance in skin and ability to produce a variety of proinflammatory mediators, we propose that mast cells may play a key role in ultraviolet B ...

BACKGROUND: Lupus erythematosus profundus (LEP) is a rare variant lupus erythematosus with unclear etiology characterized by lobular panniculitis. Recently, we observed a case of LEP involving the lower right eyelid. Our immunohistological analyses of lesional skin biopsies revealed a type I IFN signature in the context of cytotoxic lobular panniculitis. ...

The calcineurin inhibitor cyclosporin A and the phosphodiesterase 4 inhibitor cilomilast exhibit potent immunomodulatory properties which make them interesting therapeutics for the treatment of skin disorders like canine and human atopic dermatitis. Cyclosporin A and phosphodiesterase 4 inhibitors have already demonstrated clinical efficacy in the therapy of canine and human ...

The skin is colonized by a variety of microorganisms such as Propionibacterium acnes, Staphylococcus epidermidis and Malassezia furfur that are in a stable balance and form the resident skin flora. The homeostasis of this ecosystem is of fundamental importance as it plays a barrier role by limiting the invasion and ...

OBJECTIVE: To modify the skin window technique for extended analysis of acute inflammatory responses in humans, and demonstrate its applicability for investigating disease. SUBJECTS: 15 healthy subjects and 5 Crohn's patients. TREATMENT: Skin windows, created by dermal abrasion, were overlaid for various durations with filter papers saturated in saline, 100 ...

Cutaneous inflammatory diseases such as psoriasis vulgaris and atopic dermatitis are associated with altered keratinocyte function, as well as with a particular cytokine production profile of skin-infiltrating T lymphocytes. In this study we show that normal human epidermal keratinocytes express a functional type II oncostatin-M (OSM) receptor (OSMR) consisting of ...

Ionizing radiation exposure of skin results in a cutaneous radiation reaction comprising all pathophysiological reactions and clinical symptoms in irradiated skin. Biological responses of skin occur in a characteristic temporal pattern and mainly depend on radiation quality, dose rate, total dose, and cellular conditions. Immediately after irradiation, production of cytokines ...

Skin serves a vital role, providing protection from the broad array of pathogens present in our environment. In addition to the passive barrier functions of the skin, mammals have evolved a robust and versatile surveillance and rapid response system for recognition and elimination of invading organisms. This immune surveillance network ...

It has been well established that cytidine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODNs) activate innate and adaptive immune responses in keratinocytes by stimulating Toll-like receptor 9 (TLR9)-dependent signaling pathways. However, as Dorn et al. report, keratinocytes possess another, yet uncharacterized, TLR9-independent mechanism for the recognition of ODNs. Surprisingly, the activation of the pathway ...

The skin is constantly exposed to endogenous and environmental pro-oxidant agents, which lead to harmful generation of reactive oxygen species (ROS). Healthy skin, being a potential target for oxidative stress, is equipped with a large number of defence mechanisms including antioxidant systems. This protection can be corrupted by an imbalance ...

Studies of immune-suppressed transplant recipients and patients with biopsy-proven skin cancer have confirmed that ultraviolet (UV) radiation-induced immune suppression is a risk factor for the development of skin cancer in humans. UV radiation suppresses the immune system in several ways. The UVB spectrum inhibits antigen presentation, induces the release of ...

Mechanisms of juvenile susceptibility to cancer are not well understood. The immune response in neonates favors nonresponsiveness or T(H)2-dominant responses, raising the question of a role for neonatal immunity in this susceptibility. We have investigated the postulate that the inflammatory response differs in neonatal and adult skin. We found no ...

AIM: To describe the early pathological changes in the cornea during toxic epidermal necrolysis (TEN). METHOD: Demonstration of histological features of sequential corneal samples taken during management of complications of TEN in a young adult. RESULTS: Early vacuolation of basal keratinocytes and late infiltration of the cornea with CD 8 ...

BACKGROUND: As clinical and histological features of allergic and irritant contact dermatitis share common characteristics, the differentiation between them in the preclinical and clinical evaluations of chemicals remains difficult. OBJECTIVE: To identify the differences in the underlying immunological mechanisms of chemical-induced allergic or irritant skin responses. METHODS: We systematically studied ...