Hyaluronan regulates chemical allergen-induced IL-18 production in human keratinocytes

Nikitovic, Dragana; Berdiaki, Aikaterini; Galbiati, Valentina; Kavasi, Rafaela‐Maria; Papale, Angela; Tsatsakis, Aristidis; Tzanakakis, George N.; Corsini, Emanuela

doi:10.1016/j.toxlet.2014.09.026

Cited by 29 publications

(43 citation statements)

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“…As TLRs evolved to sense microbial pathogens, the inflammation induced by contact allergens would thus appear to be an accident in nature, but it raises the possibility that the activation of these pathways in keratinocytes and dendritic cells is a trait shared by all compounds with skin sensitizing potential. In line with these observations are our data, which show the possibility of discriminating contact allergens using the selective induction of IL-18 in keratinocytes, including reconstructed human epidermis [21,[28][29][30][31][32]. The argument is that more potent contact allergens will provoke at lower concentrations a stronger innate inflammatory reaction than will less potent allergens, which will in turn influence the migration of skin dendritic cells and their degree of activation and, therefore, the quality of immune responses elicited [33].…”

Section: New In Vitro Models and The Possibility Of Potency Assessmentsupporting

confidence: 78%

Alternative Approach for Potency Assessment: In Vitro Methods

et al. 2016

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Abstract:Over the last decade, incredible progress has been made in the development of non-animal tests to assess contact hypersensitivity. Four methods have been successfully validated and Organisation for Economic Co-operation and Development (OECD) guidelines are available or soon will be. Currently validated methods are useful for hazard identification, classification and labeling. However, to achieve a complete replacement of animals in skin sensitization assessment, dose-response information and evaluation of relative skin sensitizing potency to support effective risk assessment are necessary. In this context, potency is based on the concentration of chemicals needed to induce a positive response. This will require a better understanding of the mechanisms determining potency, including pathway analysis and marker signature identification (selection of an appropriate immune-mediated response to serve as the basis), together with quantitative and qualitative correlations between marker signatures and potency of chemicals in relation with T cell responses. This review aims to discuss the state-of-the-art in the field of in vitro assessment of the no induction sensitization level of contact sensitizers.

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Section: New In Vitro Models and The Possibility Of Potency Assessmentsupporting

confidence: 78%

Alternative Approach for Potency Assessment: In Vitro Methods

et al. 2016

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“…HA may indeed have a more critical role in the upper part of the epidermis, just below the stratum granulosum, as an additional protection layer or, once degraded by various invaders, as a damage-associated molecular pattern (42). Further studies are needed to unravel these roles of HA in the skin.…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan Does Not Regulate Human Epidermal Keratinocyte Proliferation and Differentiation

Malaisse

Pendaries

Hontoir

et al. 2016

Journal of Biological Chemistry

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Hyaluronan (HA) is synthesized by three HA synthases (HAS1, HAS2, and HAS3) and secreted in the extracellular matrix. In human skin, large amounts of HA are found in the dermis. HA is also synthesized by keratinocytes in the epidermis, although its epidermal functions are not clearly identified yet. To investigate HA functions, we studied the effects of HA depletion on human keratinocyte physiology within in vitro reconstructed human epidermis. Inhibition of HA synthesis with 4-methylumbelliferone (4MU) did not modify the expression profile of the epidermal differentiation markers involucrin, keratin 10, and filaggrin during tissue reconstruction. In contrast, when keratinocytes were incubated with 4MU, cell proliferation was decreased. In an attempt to rescue the proliferation function, HA samples of various mean molecular masses were added to keratinocyte cultures treated with 4MU. These samples were unable to rescue the initial proliferation rate. Furthermore, treatments with HA-specific hyaluronidase, although removing almost all HA from keratinocyte cultures, did not alter the differentiation or proliferation processes. The differences between 4MU and hyaluronidase effects did not result from differences in intracellular HA, sulfated glycosaminoglycan concentration, apoptosis, or levels of HA receptors, all of which remained unchanged. Similarly, knockdown of UDP-glucose 6-dehydrogenase (UGDH) using lentiviral shRNA effectively decreased HA production but did not affect proliferation rate. Overall, these data suggest that HA levels in the human epidermis are not directly correlated with keratinocyte proliferation and differentiation and that incubation of cells with 4MU cannot equate with HA removal. Hyaluronan (HA),2 a large polysaccharide of the extracellular space, is composed of repetitive D-glucuronic acid and D-Nacetylglucosamine dimer units. Although it belongs to the glycosaminoglycan (GAG) family, HA is not synthesized in the Golgi network; the molecule is assembled at the inner face of the plasma membrane, and the newly formed polymer is extruded into the extracellular matrix as it lengthens by addition of the dimer units. This mechanism allows the formation of huge HA molecules with masses ranging from 10 5 to 10 7 Da and lengths ranging from 2 to 25 m (1).HA synthesis is performed by three different glycosyltransferases called hyaluronan synthases (HAS) located at the plasma membrane. These three enzymes, HAS1, HAS2, and HAS3, differ from each other with respect to temporal expression pattern during development, specific activity, and size of HA polymers generated (2, 3). The degradation of HA is carried out in somatic tissues by HYAL1 and HYAL2, two enzymes belonging to the hyaluronidase family (4).HA has been identified in most tissues of the organism. Half of the total amount of HA is localized in skin (5). The skin is a large organ making up the first barrier against physical, biological, and chemical damages to the body. In the dermis, the main cell type is represented by fibroblasts, which...

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“…It has been reported that contact sensitizer with 2, 4, 6-trinitrochlorobenzene (TNCB) induced increase of hyaluronidase activity and breakdown of the extracellular matrix component HA to pro-inflammatory low molecular weight fragments in the ear skin [5]. Furthermore, in an in vitro model of human keratinocytes, DNCB treatment was shown to stimulate hyaluronidase 1 and 2 expressions inducing HA degradation [20]. These findings suggested a beneficial role for hyaluronidase inhibitors in prevention and treatment of experimental dermatitis.…”

Section: Bmentioning

confidence: 94%

Competitive Inhibition of Mammalian Hyaluronidase by Tomato Saponin, Esculeoside A

Zhou

Kimura

Nohara

et al. 2018

Natural Product Communications

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Esculeoside A, a glycoside of spirosolane-type, is identified as a major component in ripe tomato fruits. Our previous study showed that esculeoside A inhibited hyaluronidase activity in vitro and ameliorated experimental dermatitis in vivo. The aim of this present study is to investigate the inhibition mode on mammalian hyaluronidase by esculeoside A. Measured by a modified Morgan-Elson method, the present kinetic analysis of the hydrolysis reaction using hyaluronic acid revealed that no significant difference was observed in velocity maximum V max , and Michaelis-Menten constant K m was shown as 0.74 mM in the absence of esculeoside A, was increased as 1.32 and 1.98 mM with 3 and 30 μM of esculeoside A, respectively. Thus suggested that the inhibition mode on hyaluronidase by esculeoside A was competitive. This competitive inhibition on hyaluronidase activity may become valuable in the amelioration of mice experimental dermatitis by esculeoside A.

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Hyaluronan regulates chemical allergen-induced IL-18 production in human keratinocytes

Cited by 29 publications

References 50 publications

Alternative Approach for Potency Assessment: In Vitro Methods

Alternative Approach for Potency Assessment: In Vitro Methods

Hyaluronan Does Not Regulate Human Epidermal Keratinocyte Proliferation and Differentiation

Competitive Inhibition of Mammalian Hyaluronidase by Tomato Saponin, Esculeoside A

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