ABSTRACT
Loss-of-function mutations of filaggrin (FLG) gene (FLG) are the strongest known genetic risk factor for atopic dermatitis (AD). It is still debatable how FLG gene mutations and the resulting abnormal amount of FLG protein contribute to skin barrier function and symptoms of AD. In this study, we examined the effects of loss-of-function mutations of FLG gene on the severity of skin lesions and skin barrier function in 55 patients with AD by evaluating eight patients with AD with FLG gene mutations and 47 patients with AD without mutations. The results showed that the FLG gene mutation did not affect the duration of AD, severity of AD, degree of local inflammatory symptoms, skin water content and trans-epidermal water loss of the lesions. Next, in these eight mutation carriers and the 47 non-carriers, stratum corneum was collected from the three site of skin lesions using tape-stripping method, and the amounts of FLG protein and total amino acid contained in the stratum corneum was measured to investigate the effect of the FLG gene mutation on the amount of FLG gene product in the local lesion. FLG abnormalities had little effect on FLG protein and total amino acid content in the stratum corneum in the lesional skin. The amount of the FLG products, especially amino acids derived from FLG, in the stratum corneum of AD lesional skin is influenced by development of dermatitis. The results obtained from this study supports that the activation of Th2-dominant inflammatory cells, together with FLG abnormality, plays a role in suppressing the production of FLG in skin lesions.
Subject(s)
Dermatitis, Atopic , Dermatitis, Atopic/genetics , Filaggrin Proteins , Genotype , Humans , Intermediate Filament Proteins/genetics , Mutation , Severity of Illness IndexSubject(s)
Dermatitis, Atopic/diagnosis , Epidermis/pathology , Severity of Illness Index , Toll-Like Receptor 3/metabolism , Adult , Biomarkers/blood , Biomarkers/metabolism , Case-Control Studies , Dermatitis, Atopic/blood , Dermatitis, Atopic/pathology , Eosinophils , Female , Healthy Volunteers , Humans , Leukocyte Count , Male , Middle Aged , Young AdultABSTRACT
Investigation of collagenase inhibitory natural components afforded two quinic acid esters (1 and 2) and quercetin (3) from the leaves of Pluchea indica (Compositae). Of these, compounds 1 and 2 exhibited collagenase inhibitory activity (IC(50)) at a concentration of less than 10 microm, and 1 showed matrix metalloproteinase (MMP)-2 and -9 inhibitory activity (IC(50)) at 2.5 and 6.4 microm, respectively.
