Previous studies revealed that prostaglandins contribute to the mechanism of maintenance of gastrointestinal integrity and mediate various physiological aspects of mucosal defense. The suppression of prostaglandin synthesis in the stomach is a critical event in terms of the development of mucosal injury after administration of various NSAID including aspirin (ASA). ...

Life-threatening gastrointestinal (GI) diseases of prematurity are highly associated with systemic candidiasis. This implicates the premature GI tract as an important site for invasion by Candida. Invasive interactions of Candida spp. with immature enterocytes have heretofore not been analyzed. Using a primary immature human enterocyte line, we compared the ability ...

Lymphocyte migration (homing) to specific tissues has an important role during protective and pathological immune responses, including inflammatory bowel diseases. Lymphocytes use integrin α4β7 and the chemokine receptor CCR9 to localize to the gastrointestinal mucosa; their respective ligands, mucosal addressin cell adhesion molecule-1 and CCL25, are displayed on endothelial cells ...

Context: No previous study determined monocyte- and lymphocyte-suppressing effects of levothyroxine and selenomethionine and assessed whether their coadministration is superior to treatment with only one of these drugs. Objective: Our objective was to compare the effect of levothyroxine and selenomethionine on monocyte and lymphocyte cytokine release and systemic inflammation in ...

Wound healing is an appropriate response to inflammation and tissue injury in the gastrointestinal tract. If wound healing responses are excessive, perpetuated or prolonged, they lead to fibrosis, distortion of tissue architecture and loss of function. This introductory editorial and mini-reviews or reviews in this themes series highlight the diversity ...

IFN-α is known to play a key role in autoimmunity, but the mechanisms are uncertain. Although the induction of autoimmunity by IFN-α is consistent with primarily immunomodulatory effects, the high frequency of nonautoimmune inflammation suggests other mechanisms. We used thyroiditis as a model to dissect these possibilities. IFN-α treatment of ...

Acute myocardial infarction (MI) involves necrotic and apoptotic loss of cardiomyocytes. One strategy to salvage ischemic cardiomyocytes is to modulate gene expression to promote cell survival without disturbing normal cardiac function. MicroRNAs (miRNAs) have emerged as powerful regulators of multiple cellular processes, including apoptosis, suggesting that regulation of miRNA function ...

BACKGROUND: Estrogens are classified as type I (planar) and type II (angular) based on their structures. In this study we have used triphenylethylenes (TPEs) compounds related to 4OHT to address the hypothesis that the conformation of the liganded estrogen receptor (ERα) may dictate the E2-induced apoptosis of the ER+ breast ...

Graves' disease (GD) is a chronic autoimmune process in the thyroid gland and involves IFN and IFN driven immune activation. Assuming the thyroid gland is the main site stimulating the autoimmune response, we investigated the role of IFNs and other factors in the chronic evolution of GD by comparing the ...

Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in the catabolism of heme, followed by production of biliverdin, free iron and carbon monoxide (CO). HO-1 is a stress-responsive protein induced by various oxidative agents. Recent studies demonstrate that the expression of HO-1 in response to different inflammatory mediators may contribute to ...

Increasing evidence suggests that pro-inflammatory cytokines are at play in lowering peripheral thyroid hormone levels during critical illness. Conversely, thyroid hormones have been suggested to enhance production of inflammatory cytokines. In view of these considerations, we hypothesized a mutual association between triiodothyronine and pro-inflammatory cytokines. Therefore we evaluated the relation ...

Activation of innate and acquired immune responses, which can be induced by infection, inflammation, or tissue injury, may impact the development of autoimmunity. Although stimulation of cells by double-stranded DNA (dsDNA) has been shown to activate immune responses, the role of self-genomic DNA fragments released in the context of sterile ...

The skin has long been recognized as a prominent target tissue in systemic lupus erythematosus (SLE) which plays a crucial role in the initiation and perpetuation of the autoimmune reaction cascade as a consequence of ultraviolet (UV)-induced keratinocyte apoptosis. Antibodies against IFI16 (interferon-inducible protein 16) have been detected in the ...

Death receptor-mediated apoptosis has been implicated in target organ destruction in patients with chronic autoimmune thyroiditis. Several apoptosis signaling pathways, such as Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), have been shown to be active in thyroid cells and may be involved in destructive thyroiditis. Thyroid toxicity of ...

Increased iodide intake has been linked to the development of hypothyroidism and/or autoimmune thyroiditis in humans and animals, but the mechanisms involved remain poorly understood. Increased ingestion of iodide is likely to have pleiotropic effects on either metabolic or immunological processes. Within the latter domain, recent interest has been focused ...

Psoriasis is one of the commonest chronic inflammatory disorders. Its cause is unknown, but a wealth of studies indicate that the disease results from a complex and dynamic interplay between genetic and environmental factors that trigger an excessive inflammatory response in the skin. Dendritic cells and effector T-cells are central ...

Autoimmune thyroiditis is one of common organ-specific autoimmune disease. The aim of this study was to observe the effect of adipose tissue derived mesenchymal stem cells (ATMSC) and CTLA4Ig gene-transduced ATMSC on autoimmune thyroiditis. Experimental autoimmune thyroiditis was induced by immunization with thyroglobulin. Animals were divided into three groups: (i) ...

Thyroglobulin (Tg) represents one of the largest known self-antigens involved in autoimmunity. Numerous studies have implicated it in triggering and perpetuating the autoimmune response in autoimmune thyroid diseases (AITD). Indeed, traditional models of autoimmune thyroid disease, experimental autoimmune thyroiditis (EAT), are generated by immunizing mice with thyroglobulin protein in conjunction ...

There is growing evidence that the cannabinoid CB(1) receptor antagonist, rimonabant (SR141716) exerts potential anti-proliferative and anti-inflammatory actions. Here, we have assessed the effects of rimonabant in vitro in murine immortalized keratinocytes and in vivo by assaying the topical anti-inflammatory activity. Cell viability and death in a keratinocyte cell line ...

Background: Dendritic cells (DCs) are the most effective antigen-presenting cells and key regulators of immune response. The immunoregulatory properties of DCs strongly depend on the microenvironment in which DCs have been matured and activated. Thyroid hormones are an important part of this environment and regulate many vital processes including growth ...

The gastrointestinal tract provides a variety of environmental challenges to any bacterium seeking to successfully colonize or cause disease in a host. A major obstacle is the varied oxygen concentrations encountered at different sites in the intestine. Here we review the mechanisms bacterial pathogens utilize to sense oxygen within the ...

Trans-urocanic acid is isomerized to cis-urocanic acid (C-UCA) by ultraviolet radiation. C-UCA suppresses immunity in vitro and in vivo in animals; its effect on human skin is unknown. We sought to determine whether its topical application to normal skin suppresses induction of immunity to dinitrochlorobenzene (DNCB). Forty subjects applied C-UCA ...

Skin fibrosis, in its mildest form, may present only a minor aesthetic problem, but in the most severe cases it can lead to debilitating pathologies of the skin, for example keloid and hypertrophic scars, and systemic sclerosis. In recent years, extensive basic research aimed at understanding the molecular mechanisms underlying ...

Three different suture patterns (simple interrupted, interrupted horizontal mattress, subcuticular) were placed in a full thickness incision (skin and body wall) of 18 goldfish (Carassius auratus). After 14 days all fish were euthanized using benzocaine solution. The tissue reactions were evaluated by gross visual inspection and histopathological examination. The superficial ...

Psoriatic plaques present a complex expression profile, including high levels of cytokines, chemokines and growth factors. Circulating cytokines have been suggested to reflect the activation status of the inflammatory process. To analyse 20 cytokines, chemokines and growth factors in 14 patients with psoriasis vulgaris at the start and during the ...

Staphylococcus aureus heavily colonizes the lesions of patients with atopic dermatitis (AD) and is known to trigger a worsening of AD. However, the exact mechanism by which S. aureus promotes AD is unknown. Thymic stromal lymphopoietin (TSLP), which is highly expressed by keratinocytes in skin lesions of patients with AD ...

Atopic dermatitis is characterized by scratching and by T(H)2-dominated immune response to cutaneously introduced antigens. Antigen application to skin mechanically injured by tape stripping results in T(H)2-dominated skin inflammation. To examine the effect of tape stripping on the capacity of skin dendritic cells (DCs) to polarize T cells toward a ...

Placenta extract features as a composition of ointments used for skin beautification, dermatological diseases and skin dryness. However, little evidence has been cited about its underlying mechanisms of action by which it exerts a beneficial role in dermatological diseases in vivo. In this study, we intended to test the effect ...

Solar ultraviolet radiation (UVR) is well known for its immunosuppressive properties. UVR can suppress immune reactions both in a local and a systemic fashion. One of the major molecular mediators of photoimmunosuppression is UVR-induced DNA damage. In contrast to immunosuppressive drugs, UVR does not act in a general but antigen-specific ...

Psoriasis is a common chronic skin disease characterized by recurrent erythromatous skin plaques that exhibit epidermal hyperplasia, variable inflammatory cell infiltrate, and abnormalities of the dermal vascularization. The involvement of angiogenic growth factors such as vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs) and inflammatory cytokines such as IFNγ, IL-1, ...

Exposing skin to ultraviolet (UV) radiation contributes to photoaging and to the development of skin cancer by DNA lesions and triggering inflammatory and other harmful cellular cascades. The present study tested the ability of unique lipid molecules, polyhydroxylated fatty alcohols (PFA), extracted from avocado, to reduce UVB-induced damage and inflammation ...

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening adverse reactions, which could be induced by a variety of drugs. It was proposed that human leukocyte antigen (HLA)-restricted presentation of antigens (drugs or their metabolites) to T lymphocytes initiates the immune reactions of SJS/TEN. However, the genetic susceptibility and ...

Excessive sun exposure or high acute doses of ultraviolet (UV)-B radiation promote cutaneous inflammation and genetic mutations, both of which can ultimately contribute to skin carcinogenesis. A major mediator synthesized in the epidermis in response to UVB irradiation is the secosteroid hormone vitamin D(3), and as such, considerable attention is ...

Insertion of a cutaneous microdialysis catheter into normal dermis has been shown to induce the production of IL1b, IL6 and IL8 in an innate response to minimal trauma. In the present study, skin biopsy for immunohistochemistry has been performed at the site of the microdialysis catheter to compare the findings ...

There are many proposed non-antimicrobial actions of tetracyclines. Pathways affected by these medications are often overexpressed in various dermatologic conditions. Matrix metalloproteinases (MMPs) are enzymes best known for breaking down connective tissue proteins and are upregulated in conditions involving dermal destruction. Inhibition of MMPs by tetracyclines has been emphasized as ...

Interleukin-23 is a key cytokine involved in the generation of Th17 effector cells. Clinical efficacy of an anti-p40 mAb blocking both IL-12 and IL-23 and disease association with single nucleotide polymorphisms in the IL23R gene raise the question of a functional role of IL-23 in psoriasis. In this study, we ...

We show here that keratinocytic nuclear receptor retinoid X receptor-α (RXRα) regulates mouse keratinocyte and melanocyte homeostasis following acute UVR. Keratinocytic RXRα has a protective role in UVR-induced keratinocyte and melanocyte proliferation/differentiation, oxidative stress-mediated DNA damage, and cellular apoptosis. We discovered that keratinocytic RXRα, in a cell-autonomous manner, regulates mitogenic ...

Skin cancer is the most common cancer in the United States. Ultraviolet B (UVB) radiation in sunlight is the major environmental factor causing skin cancer. p21, a p53-inducible protein, plays an important role in cell cycle, DNA repair, and apoptosis. Here we have investigated the effect of UVB radiation on ...

Previously, a selection of low molecular weight contact and respiratory allergens had tested positive in both a skin and a respiratory local lymph node assay (LLNA), but formaldehyde was negative for sensitization by inhalation. To investigate whether this was due to intrinsic properties of aldehyde sensitizers, the structurally related allergen ...

Inflammation is a defensive process by which the body responds to both localized and systemic tissue damage by the induction of innate and adaptive immunity. Literature from human and animal studies links inappropriate in utero inflammation to preterm parturition and fetal injury. The pathways by which such inflammation may cause ...

The human epidermis provides a first line of defense against exogenous pathogens. Resistance to bacterial skin infections, e.g. with Staphylococcus aureus (S. aureus), is based on the function of intact innate immune mechanisms in the epidermis, mainly provided by keratinocytes. They establish the local cytokine and chemokine milieu which is necessary ...

Skin melanoma, a life-threatening disease, has a recently reported worldwide increase in incidence, despite primary prevention. Skin melanoma statistics emphasize the need for finding markers related to the immune response of the host. The mechanisms that are able to over-power the local immune surveillance comprise molecules that can be valuable ...

For many years, psoriasis was firmly believed to be a disease of epidermal keratinocytes, but now is attributed to a combination of genetic and environmental factors that promote a T-cell mediated immune response in the skin. Psoriasis is now understood to be a systemic T-cell mediated autoimmune disease with the ...

The aim of the review is to provide up-to-date information on the multiple roles of epidermal keratinocytes in the immune reactions associated with allergic contact dermatitis and atopic dermatitis skin diseases. In the last two decades, it has become clear that keratinocytes are highly active immunological cells, with major control ...

Teriflunomide (TFN) reportedly inhibits de novo pyrimidine synthesis and exhibits anti-inflammatory, disease-modifying activities in vivo. These qualities would suggest that TFN could be useful in skin cancer chemoprevention or therapy. We investigated some mechanistic aspects of this tenet by characterizing the effects of TFN on premalignant and malignant human cutaneous keratinocytes. ...

We have recently shown that commercial p-phenylenediamine (PPD)-containing hair dyes are potent immune activators that lead to severe contact hypersensitivity in an animal model. However, only a minority of people exposed to permanent hair dyes develops symptomatic contact hypersensitivity. This suggests that the majority of people exposed to hair dyes ...

Human papillomaviruses (HPVs) are small DNA viruses, which specifically infect keratinocytes at different body sites. The association between cutaneous squamous cell carcinoma (SCC) formation, ultraviolet (UV) irradiation and infection with a high-risk subset of cutaneous HPVs has been postulated although the underlying molecular mechanisms by which HPV may play a ...

Ionizing radiation is used to treat many of cancers, however, it also produces unwanted side effect on normal tissues, such as radiodermatitis. We previously established an animal model for radiodermatitis, and found that X-ray irradiation induced the expression of ID3 in hairless mouse skin by cDNA microarray. The aim of ...

Atopic dermatitis (AD) is a common skin disease associated with a T(H)2 response and increased levels of T(H)2-associated cytokines and IgE. The mechanisms resulting in skewing the immune response in a T(H)2 direction in AD are not fully elucidated. However, such skewing has recently been associated with IL-25 in a ...

Glandular Kallikrein is a serine-protease with trypsin-like activity and is able to generate bioactive peptides from inactive precursors. We have evaluated the presence of this protease in the different organs of the Atlantic salmon (Salmo salar). The results clearly indicate that GK and PRL are generated in the same pituitary ...