Inflammatory plasma signature of chronic hand eczema: Associations with aetiological and clinical subtypes.

BACKGROUND: Chronic hand eczema (CHE) is a highly prevalent, heterogeneous, skin disease that encompasses different aetiological and clinical subtypes. Severe CHE without atopic dermatitis has been associated with systemic inflammation; yet it remains unknown if specific CHE subtypes leave distinct, systemic, molecular signatures. OBJECTIVES: To characterize the inflammatory plasma signature of different aetiological and clinical CHE subtypes. METHODS: We assessed expression levels of 266 inflammatory and cardiovascular disease risk plasma proteins as well as filaggrin gene mutation status in 51 well-characterized CHE patients without concomitant atopic dermatitis and 40 healthy controls. Plasma protein expression was compared between aetiological and clinical CHE subgroups and controls both overall and according to clinical CHE severity. Correlation analyses for biomarkers, clinical and self-reported variables were performed. RESULTS: Very severe, chronic allergic contact dermatitis (ACD) on the hands was associated with a mixed Type 1/Type 2 systemic immune activation as compared with controls. Circulating levels of Type 1/Type 2 inflammatory biomarkers correlated positively with clinical disease severity among CHE patients with ACD. No biomarkers were found, that could discriminate between aetiological subtypes, for example, between ACD and irritant contact dermatitis. Hyperkeratotic CHE showed a distinct, non-atopic dermatitis-like, systemic footprint with upregulation of markers associated with Type 1 inflammation and tumour necrosis factor alpha, but not Type 2 inflammation. Increased levels of CCL19 and CXCL9/10 could discriminate hyperkeratotic CHE from both vesicular and chronic fissured CHE, whereas no difference was found between the latter two subtypes. CONCLUSION: Profiling of systemic biomarkers showed potential for identifying certain CHE subtypes. Peripheral blood levels of inflammatory biomarkers were associated and correlated with the clinical disease severity of chronic ACD on the hands, underlining that this is a systemic disease. We question whether hyperkeratotic CHE should be classified as eczema.

IL-26 in allergic contact dermatitis: Resource in a state of readiness.

In this study, we investigated the role of IL-26 in allergic contact dermatitis (ACD), highlighting its' contribute in the cytotoxic mechanism responsible for the tissue injury. IL-26 is a signature Th17 cytokine, and immune cells are its predominant sources. Recently, it has shown that Th17 cell-derived-IL-26 functions like an antimicrobial peptide. Here, we hypothesized that IL-26 could be involved in cytotoxicity mechanism that underlies ACD. Indeed, we have attributed a role to IL-26 in this context, through PBMC cytotoxicity assays vs HaCat. To demonstrate that IL-26 was effectively involved in this activity, we performed the assay using transfected ACD PBMCs by siRNA for IL-26. Indeed, we demonstrated that these cells were less able to kill keratinocytes compared with ACD PBMCs (P < .01). In conclusion, our findings support the idea that this emergent cytokine, IL-26, is implicated in the killing mechanisms of KC observed during ACD.

Silkworm dropping extract ameliorate trimellitic anhydride-induced allergic contact dermatitis by regulating Th1/Th2 immune response.

Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by hapten-specific immune response. Silkworm droppings are known to exert beneficial effects during the treatment of inflammatory diseases. Here, we studied whether topical treatment and oral administration of silkworm dropping extract (SDE) ameliorate trimellitic anhydride (TMA)-induced ACD. In ACD mice model, SDE treatment significantly suppressed the increase in both ear thickness and serum IgE levels. Furthermore, IL-1ß and TNF-α levels were reduced by SDE. In allergic responses, SDE treatment significantly attenuated the production of the Th2-associated cytokine IL-4 in both ear tissue and draining lymph nodes. However, it increased the production of the Th1-mediated cytokine IL-12. Thus, these results showed that SDE attenuated TMA-induced ACD symptoms through regulation of Th1/Th2 immune response. Taken together, we suggest that SDE treatment might be a potential agent in the prevention or therapy of Th2-mediated inflammatory skin diseases such as ACD and atopic dermatitis. ABBREVIATIONS: ACD: allergic contact dermatitis; AD: atopic dermatitis; APC: antigen presenting cells; CCL: chemokine (C-C motif) ligand; CCR: C-C chemokine receptor; Dex: dexamethasone; ELISA: enzyme-linked immunosorbent assay; IFN: interferon; Ig: immunoglobulin; IL: interleukin; OVA: ovalbumin; PS: prednisolone; SDE: silkworm dropping extract; Th: T helper; TMA: trimellitic anhydride; TNF: tumor necrosis factor.

Histamine and Histamine Receptors in Allergic Dermatitis.

In this chapter we will first introduce the pathophysiological process of several skin diseases including allergic dermatitis, a common skin disease, including chronic allergic contact dermatitis (CACD), and atopic dermatitis (AD). In CACD and AD patients, repeated skin exposure to antigens contributes to the development of chronic eczematous lesions. Repeated application of haptens on mice allows emulation of the development of CACD in humans. Further, we will focus on H1, H2, and H4 histamine receptors and their effects on CACD and AD. Histamine-deficient mice, with a knockout histidine decarboxylase (HDC) gene, were used to investigate the role of histamine in CACD and AD. Histamine induces infiltration of inflammatory cells, including mast cells and eosinophils, and elevates Th2 cytokine levels in CACD. Histamine promotes the development of eczematous lesions, elevates IgE serum levels, and induces scratching behavior in CACD. The administration of H1 or H4 receptor antagonists was effective to ameliorate these symptoms in murine CACD models. The combination of H1 and H4 receptor antagonists is a potential therapeutic target for chronic inflammatory skin diseases such as CACD and AD, since combined therapy proved to be more effective than monotherapy.

[Prediction of occupational allergic contact dermatitis induced by formaldehyde by IL17/IL22 secretion cell rest combined with patch test].

Objective: To investigate the possible role of IL17-and IL22-secreting cells combined with patch test for the prediction of formaldehyde-induced occupational allergic contact dermatitis(OACD). Methods: From October 2014 to October 2016, totally 131 formaldehyde-exposed workers(49 cases with inflammatory skin lesions,82 ones without inflammatory skin lesions)and 63 non-exposed health controls were recruited. Patch-test was performed in 49 cases of formaldehyde-exposed workers with inflammatory skin lesions. Circulating IL17+and IL22+Tcell subsets were assessed by flow cytometry(FCM). Results: Among 49 cases of formaldehyde-exposed workers with inflammatory skin lesions,32 cases were with positive patch-test while 17 cases with negative patch-test. The proportions of circulating CD3+CD8-IL17+ and CD3+CD8-IL22+ cells from patch-test(+) formaldehyde-exposed workers were significantly higher than that of patch-test(-)group, formaldehyde-exposed workers without skin lesions and non-exposed controls(P<0.05). The proportions of circulating CD3+CD8-IL17+ and CD3+CD8-IL22+cells from patch-test(-)group and formaldehyde-exposed workers without skin lesions were also higher than that of non-exposed controls(P<0.05). But there was no significant difference between patch-test(-)group and formaldehyde-exposed workers without skin lesions(P>0.05). Peripheral CD3+CD8+IL17+and CD3+CD8+IL22+cells were also detected in spite of small amounts. The percentages of CD3+CD8+IL17+and CD3+CD8+IL22+ cells inperipheral blood from patch-test(+)formaldehyde-exposed workers were enhanced significantly, compared to patch-test(-)group, formaldehyde-exposed workers without skin lesions and non-exposed controls(P<0.05). The proportions of circulating CD3+CD8+IL17+ and CD3+CD8+IL22+ cells from patch-test(-)group and formaldehyde-exposed workers without skin lesions were significantly higher than that of non-exposed controls(P<0.05). But there was no significant difference between patch-test(-) group and formaldehyde-exposed workers without skin lesions(P>0.05). Conclusion: The proportions of circulating IL17+ and IL22+T cells(both CD8-and CD8+)are enhanced in formaldehyde-exposed workers at proposed OEL, possibly involved in the development of formaldehyde-induced OACD.The detection of IL17-and IL22-secreting cells combined with formaldehyde patch test help to screen the workers with allergy property and prevent OACD.

Luminex LiquiChip System for the Evaluation of Cytokine Levels in Patients with Contact Dermatitis to Potassium Dichromate.

BACKGROUND: Allergic contact dermatitis (ACD) is associated with increased production of cytokines. The patch test is the "gold-standard" diagnostic method, but it poses a risk of false results. OBJECTIVE: To evaluate a novel laboratory technique, the Luminex LiquiChip, which simultaneously measures blood levels of multiple cytokines, as a diagnostic tool in patients with chrome-induced ACD. METHODS: The study group included 20 patients with ACD and relevant patch test results for potassium dichromate and 19 patients with ACD for nickel or fragrance as control. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence and absence of potassium dichromate. The Luminex LiquiChip was used to measure levels of the following cytokines: granulocyte-macrophage colony-stimulating factor, interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, interferon-γ, and tumor necrosis factor (TNF)-α. RESULTS: Potassium dichromate-stimulated PBMCs secreted significantly higher amounts of all cytokines except TNF-α than nonstimulated PBMCs. PBMCs from patients with ACD to chromium secreted significantly higher amounts of all cytokines tested, except IL-4, compared to PBMCs from patients with ACD to nickel or fragrance. CONCLUSIONS: Potassium dichromate stimulates the production of both Th1- and Th2-type cytokines in patients with chrome allergy. The Luminex LiquiChip is a promising in vitro method and may serve as a diagnostic tool for ACD.

Serum Biomarkers of Allergic Contact Dermatitis: A Pilot Study.

BACKGROUND: Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by repeated skin exposure to contact allergens. The goal of this pilot study was to identify inflammatory proteins which can serve as biomarkers for ACD. METHODS: We measured levels of 102 cytokines, chemokines, and growth factors in the sera of 16 ACD patients during acute and remission phases, and 16 healthy volunteers. RESULTS: Serum levels of adiponectin, chemokine (C-C motif) ligand 5 (CCL5), C-reactive protein (CRP), chitinase 3-like 1 (CHI3L1), complement factor D (CFD), endoglin, lipocalin-2, osteopontin, retinol-binding protein 4 (RBP4), and platelet factor 4 (PF4) were significantly higher, whereas levels of trefoil factor 3 (TFF3) were significantly lower, in ACD patients than in healthy controls. In ACD patients, serum levels of CCL5 were elevated, whereas levels of TFF3, soluble intercellular adhesion molecule-1 (sICAM-1), and platelet-derived growth factor (PDGF)-AB/BB were found to be lower during the remission phase of the disease. CONCLUSIONS: Serum levels of adiponectin, CCL5, CRP, CHI3L1, CFD, endoglin, lipocalin-2, osteopontin, RBP4, PF4, and TFF3 might be exploited as biomarkers for ACD, whereas levels of CCL5, TFF3, sICAM-1, and PDGF-AB/BB might be exploited for evaluation of disease progression and efficacy of ACD treatment.

Cutaneous exposure to agglomerates of silica nanoparticles and allergen results in IgE-biased immune response and increased sensitivity to anaphylaxis in mice.

BACKGROUND: The skin is a key route of human exposure to nanomaterials, which typically occurs simultaneously with exposure to other chemical and environmental allergen. However, little is known about the hazards of nanomaterial exposure via the skin, particularly when accompanied by exposure to other substances. RESULTS: Repeated topical treatment of both ears and the shaved upper back of NC/Nga mice, which are models for human atopic dermatitis (AD), with a mixture of mite extract and silica nanoparticles induced AD-like skin lesions. Measurements of ear thickness and histologic analyses revealed that cutaneous exposure to silica nanoparticles did not aggravate AD-like skin lesions. Instead, concurrent cutaneous exposure to mite allergens and silica nanoparticles resulted in the low-level production of allergen-specific IgGs, including both the Th2-related IgG1 and Th1-related IgG2a subtypes, with few changes in allergen-specific IgE concentrations and in Th1 and Th2 immune responses. In addition, these changes in immune responses increased the sensitivity to anaphylaxis. Low-level IgG production was induced when the mice were exposed to allergen-silica nanoparticle agglomerates but not when the mice exposed to nanoparticles applied separately from the allergen or to well-dispersed nanoparticles. CONCLUSIONS: Our data suggest that silica nanoparticles themselves do not directly affect the allergen-specific immune response after concurrent topical application of nanoparticles and allergen. However, when present in allergen-adsorbed agglomerates, silica nanoparticles led to a low IgG/IgE ratio, a key risk factor of human atopic allergies. We suggest that minimizing interactions between nanomaterials and allergens will increase the safety of nanomaterials applied to skin.

Long-term allergic dermatitis caused by sevoflurane: a clinical report.

BACKGROUND: Allergy to volatile anaesthetics is extremely rare, but capable of damaging the professional career. METHODS: This article presents the case of a 60-year-old surgeon who developed a skin rash on the reverse of hands, which progressively worsened and extended to distant fold areas. Blood tests were normal but for eosinophilia and risen total IgE, with normal specific globulins and skin prick tests for common allergens. After 8 years, a malfunction in the anaesthetic gas scavenging system was found, and symptoms remitted within a week following its replacement. Repeated open application test with sevoflurane led to the appearance of the same lesions in the tested areas and in distant body folds. RESULTS: We hypothesize that the most probable mechanism for the reaction in our patient is systemic allergic contact dermatitis, which is caused by repeated systemic exposure to a hapten that reaches the skin through haematogenous transport in a sensitized patient. CONCLUSIONS: The report aims to warn about the potential aetiological relationship between exposure to inhaled anaesthetics and allergic manifestations with cutaneous symptoms.

Genetic factors account for most of the variation in serum tryptase--a twin study.

BACKGROUND: Mast cells are involved in a number of diseases, including inflammatory diseases such as asthma. Tryptase is a known marker of mast cell burden and activity. However, little is known about the genetic influence on serum tryptase variation. Also, only few and conflicting data exist on serum tryptase in asthma. OBJECTIVE: To estimate the overall contribution of genetic and environmental factors to the variation in serum tryptase and to examine the correlation between serum tryptase and asthma, rhinitis, markers of allergy, airway inflammation, and airway hyperresponsiveness (AHR) in a sample of Danish twins. METHODS: A total of 575 twins underwent a skin prick test and had lung function, AHR to methacholine, exhaled nitric oxide and serum tryptase measured. Multiple regression and variance components models (using the statistical package SOLAR) were computed. RESULTS: Serum tryptase values were available in 569 subjects. Intraclass correlations of serum tryptase in monozygotic and dizygotic twin pairs were 0.84 and 0.42 (P < .001). Variance decomposition showed that genetic factors accounted for 82% (95% confidence interval 74-90, P < .001) of the variation in serum tryptase. Body mass index and sex, but not asthma, rhinitis, or AHR, were correlated to serum tryptase. CONCLUSION: As much as 82% of the variation in serum tryptase is due to genetic factors. Body mass index and sex, but not asthma or AHR to methacholine, correlate to serum tryptase. A genetic overlap may exist between serum tryptase and body mass index.

Skin symptoms in bakery and auto body shop workers: associations with exposure and respiratory symptoms.

PURPOSE: Despite the importance of skin exposure, studies of skin symptoms in relation to exposure and respiratory symptoms are rare. The goals of this study were to describe exposure-response relationships for skin symptoms, and to investigate associations between skin and respiratory symptoms in bakery and auto body shop workers. METHODS: Data from previous studies of bakery and auto body shop workers were analyzed. Average exposure estimates for wheat allergen and isocyanates were used. Generalized linear models were constructed to describe the relationships between exposure and skin symptoms, as well as between skin and respiratory symptoms. RESULTS: Data from 723 bakery and 473 auto body shop workers were analyzed. In total, 5.3% of bakery and 6.1% of auto body shop workers were female; subjects' mean age was 39 and 38 years, respectively. Exposure-response relationships were observed in auto body shop workers for itchy or dry skin (PR 1.55, 95% CI 1.2-2.0) and work-related itchy skin (PR 1.97, 95% CI 1.2-3.3). A possible exposure-response relationship for work-related itchy skin in bakery workers did not reach statistical significance. In both groups, reporting skin symptoms was strongly and significantly associated with reporting respiratory symptoms, both work-related and non-work-related. CONCLUSIONS: Exposure-response relationships were observed for skin symptoms in auto body shop workers. The lack of significant exposure-response associations in bakery workers should be interpreted cautiously. Workers who reported skin symptoms were up to four times more likely to report respiratory symptoms. Improved awareness of both skin and respiratory outcomes in exposed workers is needed.

Interaction between filaggrin null mutations and tobacco smoking in relation to asthma.

BACKGROUND: The mechanisms underlying the association between filaggrin (FLG) deficiency and asthma are not known. It has been hypothesized that FLG deficiency leads to enhanced percutaneous exposure to environmental substances that might trigger immune responses. We hypothesized that interactions between FLG deficiency and environmental exposures play a role in asthma development. OBJECTIVE: We sought to investigate possible interactions between FLG null mutations and tobacco smoking in relation to asthma. METHODS: A total of 3471 adults from a general population sample participated in a health examination. Lung function and serum specific IgE levels to inhalant allergens were measured, and information on asthma and smoking was obtained by means of questionnaire. Participants were genotyped for the 2 most common FLG null mutations in white subjects: R501X and 2282del4. Another Danish population was used for replication. RESULTS: The FLG null mutation genotype was significantly associated with a higher prevalence of asthma and decreased FEV(1)/forced vital capacity ratio. In logistic regression analyses with asthma as the outcome, a significant interaction was found between FLG null mutations and smoking status (P = .02). This interaction was confirmed, although it was not statistically significant, in another Danish population study. Interactions between FLG genotype and cumulated smoking exposure were found in relation to asthma (P = .03) and decreased FEV(1)/forced vital capacity ratio (P = .03). A 3-way interaction was found among FLG genotype, smoking, and asthma, suggesting that the FLG-smoking interaction mainly played a role in nonatopic subjects. CONCLUSION: FLG null mutations modified the effects of smoking on the risk of asthma. This finding might have implications for risk stratification of the population.

[Prevalence of atopic conditions in patients with occupational contact allergic dermatitis: comparison between diagnostic tool]. / Prevalenza di atopia nella dermatite allergica da contatto professionale: confronto tra tecniche diagnostiche.

BACKGROUND: Occupational allergic contact dermatitis (OACD), to which atopy contributes to a as yet unspecified degree, accounts for a considerable number of work-related diseases. OBJECTIVES: We studied the prevalence of atopy in OACD patients. We also compared the ability of prick tests and specific IgE assays to detect it. METHODS: In 329 patients diagnosed with OACD at the Occupational Medicine Unit of Cagliari University Hospital between 2000 and 2009, we aimed at detecting atopic conditions with prick tests and IgE assays specific for allergens most frequently responsible for atopic reaction. A kappa test was used to assess concordance between the two assays. The 2 test for trend was used in the analysis of prevalence of atopy by age at diagnosis. RESULTS: A positive response was more frequently detected with prick tests (35.9%) than the specific IgE assays (31%). IgE assays for all the allergens we tested were more frequently positive among males (p range = 0.001-0.037). With either test, the highest observed prevalence of a positive response was to Dermatophagoides pteronyssinus. A significantly inverse trend with increasing age in the prevalence ofpositive reaction to Dermatophagoides pteronyssinus, Phleum pratense and Olea europaea (olive) allergens was also observed. The concordance between the two tests ranged between good (Dermatophagoides pteronyssinus, Phleum pratense and Olea europaea and moderate Artemisia vulgaris (mugwort) and Parietaria judaica. CONCLUSIONS: Our results showed a prevalence of atopic conditions in 31-35.9% of OACD patients. RESULTS: with the two assays were largely consistent, indicating that both prick tests an specific IgE assays are valid diagnostic tools for atopy.

Tolerogenic effects of interferon-gamma with induction of allergen-specific interleukin-10-producing regulatory B cell (Br1) changes in non-IgE-mediated food allergy.

In this study, specific oral tolerance induction using interferon-gamma (IFN-γ) could successfully treat food allergies. Allergen-specific IL-10-producing regulatory B cell (Br1) responses are characteristic in immune tolerance of food allergies. The in-vivo effects of IFN-γ on allergen-induced changes in Br1 proportion and numbers in food allergies were investigated. Oral food challenges were conducted and 20 allergic patients to cow's milk were selected. Of these 20 patients, five were treated with IFN-γ and milk (SOTI group), five were treated with only milk, five were treated with only IFN-γ, and five did not receive any treatment. In addition, 10 milk-tolerant subjects were involved in this study. Peripheral blood mononuclear cells (PBMCs) were stimulated using casein and stained for CD5, CD19, annexin V, and IL-10 before and after treatment. Allergy tolerance was induced only in the SOTI group along with induction of allergen-induced Br1 changes. Thus, IFN-γ can show tolerogenic effects in vivo when introduced with an allergen, which may be at least partly due to its effect on allergen-induced Br1 responses.

Topical application of a phospholipid mixture purified from pig lungs ameliorates 2,4-dinitrofluorobenzene-induced allergic contact dermatitis in BALB/c mice.

This work was designed to assess the pharmacological effectiveness as a novel anti-atopic dermatitis remedy of a phopholipid mixture purified from pig lung tissues, named KT&G101, using the BALB/c mouse model of allergic contact dermatitis. Allergic contact dermatitis was induced by applying 2,4-dinitrofluorobenzene (DNFB) epicutaneously onto the dorsal skins of mice, and KT&G101 was topically applied onto the skin areas with the lesions. The topical application of KT&G101 (0.05 ml of 10 mg/ml and 20 mg/ml KT&G101, twice a day for 15 days) decreased the total IgE level elevated in the sera of mice undergoing allergic contact dermatitis. KT&G101 was also able to decrease the 2,4-dinitrophenyl (DNP)-specific IgE level elevated in the sera of the model mice. It reduced the incidences of scratching behaviors in the mice undergoing DNFB-induced allergic contact dermatitis. It attenuated some histopathological changes, such as pustule, epidermal hyperplasia, dermatitis and fibroplasia, while it could enhance the recovery of epidermis, in the damaged skin tissues within a relatively short period after the topical application of KT&G101. KT&G101 lessened the expression of cytokines mRNAs, such as Th1-specific IL-2, TNF-ß and IFN-γ, and Th2-specific IL-4, in the mouse skin tissues showing the lesions. In brief, it is concluded that KT&G101 alleviates the symptoms involved in induced allergic contact dermatitis in BALB/c mice.

Comparative study of systemic inflammatory responses in psoriasis vulgaris and mild to moderate allergic contact dermatitis.

BACKGROUND: Psoriasis vulgaris (PV) is associated with low-grade systemic inflammation. OBJECTIVE: Cytokines' and growth factors' serum patterns in patients with PV, allergic contact dermatitis (ACD) and healthy subjects were investigated to describe and compare systemic inflammatory responses in these diseases. METHODS: A total of 12 inflammation-sensitive biomarkers were analyzed simultaneously by means of the Evidence Investigator™ biochip technology. RESULTS: In PV, proinflammatory tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukins (IL)-1ß, -2, -6, -8, and monocyte chemoattractant protein (MCP)-1 were elevated. In ACD, 2 markers, TNF-α and MCP-1, were increased, and regulatory cytokine IL-10 was decreased. Proinflammatory IL-2 had the strongest correlations with other pro- as well as anti-inflammatory cytokines in PV and ACD, whilst IL-6 correlated positively with the Psoriasis Area and Severity Index. Growth factors' levels correlated with MCP-1, but only in PV. CONCLUSION: Although psoriasis induces a more variegated proinflammatory systemic response, ACD is likewise associated with a systemic increase in inflammatory mediators.

Antigen-specific induction of osteopontin contributes to the chronification of allergic contact dermatitis.

Allergic contact dermatitis is a T cell-mediated immune response, which in its relapsing chronic form is of high socioeconomic impact. The phosphoglycoprotein osteopontin (OPN) has chemotactic and Th1 cytokine functions and in various models is essential for robust T cell-mediated immunity. Here we demonstrate that OPN is abundantly expressed by both effector T cells and keratinocytes in allergic contact dermatitis lesions. T cells from nickel-allergic donors secrete high levels of OPN following antigen-specific stimulation. OPN may substitute for missing IFN-gamma secretion in T effector cells because low IFN-gamma-producing T cell clones secrete high levels of OPN, and OPN down-modulates their interleukin-4 expression. Furthermore, interferon-gamma from T effector cells augments OPN in allergic contact dermatitis by inducing OPN in keratinocytes, which in turn polarizes dendritic cells and attracts inflammatory cells. In the murine contact hypersensitivity (CHS) model for allergic contact dermatitis, OPN is strongly induced in antigen-specific proliferating T cells, and OPN null mice display a reduced chronic CHS inflammatory response due to a decreased influx of effector T cells. Importantly, because of its function for chronic allergic contact dermatitis, OPN may well be a therapeutic target, because anti-OPN antibody treatment in part suppresses established chronic CHS.

Melatonin prevents allergic airway inflammation in epicutaneously sensitized mice.

PURPOSE: The pathological process of atopic dermatitis (AD) progressing into other types of allergic diseases such as asthma and allergic rhinitis during the first several years of life is often referred to as the atopic march. Although the phenomenon of atopic march has been recognized for decades, how asthma stems from AD is still not fully understood, confounding a universal strategy to effectively protect people from the atopic march. METHODS: We established experimental atopic march mice by first inducing allergic dermatitis with 0.5% fluorescein isothiocyante (FITC) applied to the skin, followed by an ovalbumin (OVA) airway challenge. In addition, by examining serum immunoglobulin (Ig) concentrations, airway cytokines, the levels of oxidative stress markers, histopathological changes in lung tissue and airway hyperresponsiveness (AHR), we were able to validate the successful establishment of the model. Furthermore, by detecting the attenuating effects of melatonin (MT) and the levels of oxidative stress in the atopic march mice, we explored the potential molecular mechanisms involved in the development of atopic march. RESULTS: By successfully establishing an experimental atopic march mouse model, we were able to demonstrate that overproduction of oxidative stress in the lung significantly up-regulated the activation of nuclear factor-κB (NF-κB) signaling pathways causing thymic stromal lymphopoietin (TSLP) release, which further promotes the development of atopic march. CONCLUSIONS: To mitigate the development of the atopic march, antioxidants such as MT may be imperative to inhibit NF-κB activation in the lung, especially after the onset of AD.