Modulation of the pro-inflammatory cytokines and matrix metalloproteinases production in co-cultivated human keratinocytes and melanocytes (original) (raw)

Modulation of keratin 1, 10 and involucrin expression as part of the complex response of the human keratinocyte cell line HaCaT to ultraviolet radiation

Interdisciplinary toxicology, 2013

Skin exposure to ultraviolet (UV) light evokes a complex stress response in keratinocytes. Keratin filament organization provides structural stability and mechanical integrity of keratinocytes. Involucrin is a transglutaminase substrate protein contributing to the formation of insoluble cornified envelopes. However, a more complex role for keratins and involucrin has been proposed, including the regulation of cell stress response. The aim was to evaluate modulations of keratin 1, 10 and involucrin expression in HaCaT in the light of the complex response of these cells to UV-B radiation, including effects on c-Jun and matrix metalloproteinase 1 (MMP-1) gene expression and production of interleukin (IL) 6 and 8. A UV-B (300±5 nm) dose of 10 mJ/cm(2) was selected since this dose resulted in a partial decrease in cell viability in contrast to higher UV-B doses, which induced complete cell death 48 h after treatment. The UV-B radiation induced significant expression of keratin 1 and 10 a...

Immunohistochemical analysis of in vivo UVB-induced secretion of IL-1α and IL-6 in keratinocytes

Molecular medicine reports

Keratinocytes play an important role in the inflammatory response of the skin. UVB stimulates keratinocytes to secrete several cytokines. To our knowledge, there are no reports that have examined which layer or cell type is responsible for producing these cytokines. Thus, in this study we performed immunohistochemical experiments to determine the potential cells or layers that express interleukin (IL)-1 and IL-6. The results show that the expression of IL-1α and IL-6 was induced 3 and 6 h after irradiation, respectively. Furthermore, IL-1α was maximally expressed earlier than IL-6, suggesting that IL-1α exists in the cytokine cascade of the UVB response upstream of IL-6. In addition, IL-1α expression began in the upper layers of the epidermis, whereas all layers expressed IL-6. This study provides further insight into the roles of cytokines in UVB-induced skin inflammation.

Ultraviolet radiation induces Melan-A-expressing cells in interfollicular epidermis in wild-type mice

Archives of dermatological research, 2018

Adult wild-type mice are not supposed to be proper models for ultraviolet radiation (UVR)-induced melanoma since melanocytes are confined to hair follicles and cannot be sufficiently reached by UVR. On the other hand, in mutated mouse models used for melanoma research limitations, including an altered immune system and selection of affected pathways, lead to tumors phenotypically quite different from naturally occurring melanomas. We compared the distribution of epidermal melanocytes in UVR and not-UVR-exposed wild-type C57BL/6 mice. Starting at the age of 8 weeks, mice were exposed to physiologic doses of UVR three times weekly over 16 weeks. Back skin biopsies were taken 4, 8, 12 and 16 weeks after initiation of exposure, and stained for Melan-A, representing a highly selective marker for melanocytes. Surprisingly, after exposure to UVR, Melan-A positive cells were detected also in the interfollicular epidermis of C57BL/6 mice. We conclude that UVR is capable of inducing interfoll...

Influence of cytokines on matrix metalloproteinases produced by fibroblasts cultured in monolayer and collagen gels

Journal of the Formosan Medical Association = Taiwan yi zhi, 2001

Extracellular matrix metalloproteinases (MMPs) are crucial factors involved in connective tissue remodeling that accompanies ultraviolet radiation-induced actinic damage. This study investigated whether the cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-10 modulate the expression of MMPs in cultured human newborn skin fibroblasts. Different concentrations of TNF-alpha, IL-1 beta, and IL-10 were added to human dermal fibroblasts grown in monolayers or embedded in three-dimensional (3D) collagen gels, a model closer to skin. Supernatant from the fibroblast cell culture was collected 24 hours later. The concentrations of MMP-1 and MMP-3 were assaysed by enzyme-linked immunosorbent assay (ELISA) while the concentrations of MMP-2 and MMP-9 were analysed by zymography. Basal production of MMPs was significantly greater in fibroblasts grown in 3D gels than in cells grown as monolayers. TNF-alpha and IL-1 beta induced increases in the concentrations of MMP-1, M...