ABSTRACT
Abundant corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum. To dissect the etiological role of NMFs and filaggrin deficiency in surface texture alterations, we examined mouse models with genetic deficiencies in the synthesis or degradation of filaggrin monomers for NMFs, cell stiffness (elastic modulus) and corneocyte surface protrusion density (dermal texture index). Five neonatal and adult mouse models carrying inactivating mutations of SASPase (Sasp-/-), filaggrin (Flgft/ft and Flg-/-), filaggrin-hornerin (FlgHrnr-/-), and bleomycin hydrolase (Blmh-/-) were investigated. Sasp-/- and Flg-/- were on the hairless mouse background. Atomic force microscopy was used to determine elastic modulus and dermal texture index. Corneocytes of each neonatal as well as hairless adult knockout mouse exhibited an increased number of protrusions and decreased elastic modulus. In these mice, NMFs were reduced except for Sasp-/-. Dermal texture index was inversely correlated with NMFs and elastic modulus. Our findings demonstrate that any filaggrin-NMF axis deficiency can affect corneocyte mechanical properties in mice and likely in humans. Differences in NMFs and corneocyte surface texture between neonatal and adult as well as hairless and hairy mice emphasize the need for carefully selecting the most appropriate animal models for studies.
Subject(s)
Dermatitis, Atopic/pathology , Epidermal Cells/pathology , Epidermis/pathology , Intermediate Filament Proteins/deficiency , Animals , Aspartic Acid Endopeptidases/genetics , Cysteine Endopeptidases/genetics , Dermatitis, Atopic/genetics , Disease Models, Animal , Elastic Modulus , Epidermal Cells/ultrastructure , Filaggrin Proteins , Humans , Intermediate Filament Proteins/genetics , Loss of Function Mutation , Mice , Mice, Knockout , Microscopy, Atomic ForceABSTRACT
Contact sensitization is common and affects up to 20% of the general population. The clinical manifestation of contact sensitization is allergic contact dermatitis. This is a clinical expression that is sometimes difficult to distinguish from other types of dermatitis, for example irritant and atopic dermatitis. Several studies have examined the pathogenesis and severity of allergic contact dermatitis by measuring the absence or presence of various biomarkers. In this review, we provide a non-systematic overview of biomarkers that have been studied in allergic contact dermatitis. These include genetic variations and mutations, inflammatory mediators, alarmins, proteases, immunoproteomics, lipids, natural moisturizing factors, tight junctions, and antimicrobial peptides. We conclude that, despite the enormous amount of data, convincing specific biomarkers for allergic contact dermatitis are yet to be described.
Subject(s)
Biomarkers/analysis , Dermatitis, Allergic Contact/diagnosis , Alarmins/analysis , Antimicrobial Cationic Peptides/analysis , Bioengineering , Cytokines/analysis , Epidermis/chemistry , Genetic Markers , Humans , Immunoproteins/analysis , Peptide Hydrolases/analysis , ProteomicsABSTRACT
BACKGROUND: Atopic dermatitis (AD) appears to be more common in regions with hard domestic water and in children with a fall/winter birth. However, it is unknown whether a synergistic effect exists. OBJECTIVE: We sought to evaluate the association between domestic water hardness and season of birth, respectively, with onset of AD within the first 18 months of life in a large Danish birth cohort. METHODS: Of children from the Danish National Birth Cohort, 52,950 were included. History of physician-diagnosed AD and population characteristics were obtained from interviews. Birth data were obtained from the Civil Registration System, and domestic water hardness data were obtained from the Geological Survey of Denmark and Greenland. The relative prevalence (RP) of AD was calculated by using log-linear binomial regression. RESULTS: The prevalence of AD was 15.0% (7,942/52,950). The RP of AD was 5% (RPtrend, 1.05; 95% CI, 1.03-1.07) higher for each 5° increase in domestic water hardness (range, 6.60-35.90 German degrees of hardness [118-641 mg/L]). Although the RP of AD was higher in children with a fall (RP, 1.24; 95% CI, 1.17-1.31) or winter (RP, 1.18; 95% CI, 1.11-1.25) birth, no significant interaction was observed with domestic water hardness. The population attributable risk of hard domestic water on AD was 2%. CONCLUSION: We observed that early exposure to hard domestic water and a fall/winter birth was associated with an increase in the relative prevalence of AD within the first 18 months of life. Although the 2 exposures did not interact synergistically, a dose-response relationship was observed between domestic water hardness and AD.
