Preclinical studies of a specific PPARγ modulator in the control of skin inflammation.

Peroxisome proliferator-activated receptor γ (PPARγ) antagonizes inflammatory signals by interfering with NF-κB nuclear translocation. Consistently, PPARγ agonists have been proposed in various inflammatory skin disorders, but their wide use has been limited by severe side effects. Classes of compounds with specific PPARγ agonism have been designed to selectively target inflammatory pathways.

How peroxisomes affect aflatoxin biosynthesis in Aspergillus flavus.

In filamentous fungi, peroxisomes are crucial for the primary metabolism and play a pivotal role in the formation of some secondary metabolites. Further, peroxisomes are important site for fatty acids β-oxidation, the formation of reactive oxygen species and for their scavenging through a complex of antioxidant activities. Oxidative stress is involved in different metabolic events in all organisms and it occurs during oxidative processes within the cell, including peroxisomal β-oxidation of fatty acids.

Linking αMSH with PPARγ in B16-F10 melanoma.

We have discovered a new α-melanocyte stimulating hormone (α-MSH)/peroxisome proliferator activated receptor-γ (PPAR-γ) connection in B16-F10 cells. Both PPAR-γ up-regulation and its induction as an active transcription factor were observed in response to α-MSH. The α-MSH/PPAR-γ connection influenced both pigmentation and proliferation.

The eumelanin intermediate 5,6-dihydroxyindole-2-carboxylic acid is a messenger in the cross-talk among epidermal cells.

Interest in colorless intermediates of melanocyte metabolism has traditionally been related to their role as melanin precursors, though several lines of evidence scattered in the literature suggested that these compounds may exert an antioxidant and protective function per se unrelated to pigment synthesis. Herein, we disclose the remarkable protective and differentiating effects of 5,6-dihydroxyindole-2-carboxylic acid (DHICA), a diffusible dopachrome tautomerase (DCT)-dependent eumelanin intermediate, on primary cultures of human keratinocytes. At micromolar concentrations, DHICA induced: (a) time- and dose-dependent reduction of cell proliferation without concomitant toxicity; (b) enhanced expression of early (spinous keratins K1 and K10 and envelope protein involucrin) and late (loricrin and filaggrin) differentiation markers; (c) increased activities and expression of antioxidant enzymes; and (d) decreased cell damage and apoptosis following UVA exposure.

Azelaic acid modulates the inflammatory response in normal human keratinocytes through PPARgamma activation.

Azelaic acid (AzA), a nine-carbon dicarboxylic acid, is an agent for the topical treatment of acne. It has also been shown to be effective in rosacea; however, the mechanism of action has not been clarified. Because inflammation is a common feature of both conditions, we investigated the effects of azelaic acid on the inflammatory response of normal human keratinocytes to ultraviolet B light, which is a photosensitizer agent in rosacea.

MC1R stimulation by alpha-MSH induces catalase and promotes its re-distribution to the cell periphery and dendrites.

We demonstrated a direct correlation between melanogenic and catalase activities on in vitro and ex vivo models. Here, we investigated whether the stimulation of Melanocortin-1 Receptor (MC1R) could influence catalase expression, activity and cellular localization. For this purpose, we treated B16-F0 melanoma cells with alpha-Melanocyte Stimulating Hormone (alpha-MSH) and we showed a rapid induction of catalase through a cAMP/PKA-dependent, microphthalmia-associated transcription factor (MITF) independent mechanism, acting at post-transcriptional level.

Bovine colostrum promotes growth and migration of the human keratinocyte HaCaT cell line.

Bovine colostrum represents a rich source of growth factors, which are known to play a central role in wound healing. The aim of our study was to investigate the possible mitogenic and motogenic effects induced by colostrum on human keratinocytes. Cell proliferation evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test and 5-Bromo-2'-deoxyuridine incorporation revealed that colostrum exerts a growth promoting activity.

A kindred with familial progressive hyperpigmentation-like disorder: implication of fibroblast-derived growth factors in pigmentation.

Two patients with a generalized, progressive dyschromatosis disorder are described and investigated as a model to study the role of fibroblast-derived mediators on skin pigmentation. The patients (father and daughter) had had a widespread hyperpigmentation since early life which then progressively worsened with the appearance of hyperpigmented macules, café-au-lait macules and freckles, also involving the lips, palms and soles, intermixed with small hypopigmented spots. These features resembled those of familial progressive hyperpigmentation (FPH).

Keratinocyte growth factor down-regulates intracellular ROS production induced by UVB.

Background: Exposure to ultraviolet (UV) radiation causes a complex cellular response, mostly mediated by the production of reactive oxygen species (ROS), which can be counteracted by exogenous treatments and endogenous mechanisms with anti-oxidant and scavenger properties. Keratinocyte growth factor (KGF/FGF7), a member of the fibroblast growth factor family, promotes epithelial growth and differentiation and is involved in cell survival after oxidant injuries.

Objective: We analyzed the role of KGF in the control of intracellular ROS production and oxidative stress after UVB exposure on KGF receptor (KGFR) transfected cells and human immortalized and primary keratinocytes.

Ultraviolet A induced modulation of gap junctional intercellular communication by P38 MAPK activation in human keratinocytes.

Aberrant gap junctional intercellular communication (GJIC) has been implicated in tumor development and progression. UltravioletA (UVA)-induced oxidative stress has been associated with skin carcinogenesis. We report a potential link between GJIC and the cellular stress response induced by UVA in normal human keratinocytes (NHK).

Melanosome transfer promoted by keratinocyte growth factor in light and dark skin-derived keratinocytes.

The transfer of melanin from melanocytes to keratinocytes is upregulated by UV radiation and modulated by autocrine and paracrine factors. Among them, the keratinocyte growth factor (KGF/FGF7) promotes melanosome transfer acting on the recipient keratinocytes through stimulation of the phagocytic process. To search for possible differences in the melanosome uptake of keratinocytes from different skin color, we analyzed the uptake kinetics and distribution pattern of fluorescent latex beads in primary cultures of light and dark skin-derived keratinocytes stimulated with KGF and we compared the direct effect of KGF on the melanosome transfer in co-cultures of human primary melanocytes with light and dark keratinocytes.

Cortactin involvement in the keratinocyte growth factor and fibroblast growth factor 10 promotion of migration and cortical actin assembly in human keratinocytes.

Keratinocyte growth factor (KGF/FGF7) and fibroblast growth factor 10 (FGF10/KGF2) regulate keratinocyte proliferation and differentiation by binding to the tyrosine kinase KGF receptor (KGFR). KGF induces keratinocyte motility and cytoskeletal rearrangement, whereas a direct role of FGF10 on keratinocyte migration is not clearly established. Here we analyzed the motogenic activity of FGF10 and KGF on human keratinocytes.

Expression of keratinocyte growth factor and its receptor in clear cell acanthoma.

The aetiopathogenic mechanism underlying clear cell acanthoma (CCA) is not completely clear and it has been postulated that CCA and psoriasis may have a similar pathogenesis because of the common features shared by the two diseases. As it has been recently demonstrated that in psoriatic lesions the paracrine epithelial growth factors [keratinocyte growth factor (KGF)/fibroblast growth factor (FGF)-7 and FGF-10] are involved in promoting and sustaining the keratinocyte hyperproliferation, the aim of this study was to analyse the expression of KGF on CCA lesions and to search for a role of this growth factor in CCA pathogenesis. Immunohistochemical analysis showed an up-modulation of KGF in CCA, although the immunostaining was variable among the different samples collected.

Keratinocyte growth factor promotes melanosome transfer to keratinocytes.

Melanogenesis and melanosome transfer from the melanocytes to the neighboring keratinocytes are induced by ultraviolet radiation and modulated by autocrine and paracrine factors. Keratinocyte growth factor (KGF/fibroblast growth factor (FGF)7) is a paracrine mediator of human keratinocyte growth and differentiation. We evaluated the influence of KGF on melanosome transfer in co-cultures of keratinocytes and melanocytes.