Strategy to Avoid Skin Sensitization: Application to Botanical Cosmetic Ingredients

Assessment of skin sensitization potential is mandatory for ingredients dedicated to topical applications. A battery of in vitro tests covering the key steps of the Adverse Outcome Pathway (AOP) for skin sensitization has been recommended to replace animal testing. However, despite international guidelines on in vitro methods, there is no universal approach defining their combination. The purpose of this work was to assess skin sensitization of botanical ingredients relying on a previously developed in vitro testing strategy. This tool focused on complex and poorly water-soluble substances, which were not already covered. Sixteen botanical extracts were tested in a sequential approach, starting with Sens-Is, supplemented by Organization for Economic Cooperation and Development (OECD) in vitro methods when necessary. The results on the selected well-known botanical sensitizers complemented the relevance of the strategy. Testing on experimental botanicals could detect skin sensitizers. In addition, phytochemistry was a determining support to identify and remove the components at the origin of the effect. Altogether, these results enlarged the scope of the methodology to various ingredient categories and chemical natures, contributing to place on the market new ingredients, safe for workers and end-users

Strategy to Avoid Skin Sensitization: Application to Botanical Cosmetic Ingredients

Assessment of skin sensitization potential is mandatory for ingredients dedicated to topical applications. A battery of in vitro tests covering the key steps of the Adverse Outcome Pathway (AOP) for skin sensitization has been recommended to replace animal testing. However, despite international guidelines on in vitro methods, there is no universal approach defining their combination. The purpose of this work was to assess skin sensitization of botanical ingredients relying on a previously developed in vitro testing strategy. This tool focused on complex and poorly water-soluble substances, which were not already covered. Sixteen botanical extracts were tested in a sequential approach, starting with Sens-Is, supplemented by Organization for Economic Cooperation and Development (OECD) in vitro methods when necessary. The results on the selected well-known botanical sensitizers complemented the relevance of the strategy. Testing on experimental botanicals could detect skin sensitizers. In addition, phytochemistry was a determining support to identify and remove the components at the origin of the effect. Altogether, these results enlarged the scope of the methodology to various ingredient categories and chemical natures, contributing to place on the market new ingredients, safe for workers and end-users

Rôle des Lymphocytes T régulateurs dans la progression de la fibrose hépatique associée à l'infection par le VHC.

Hepatitis C virus (HCV) becomes chronic in about 85 % of infected individuals, whereas only 15 % of infected people clear spontaneously the virus. The progression of hepatitis C to chronic status is associated to a profound down-regulation of CD4 and CD8 multispecific immune response. This immune defect may participate to the immune tolerance of VHC and consequently to its persistence. Recent findings indicate that T regulatory cells as Tr1 play an inhibitory role on T helper responses notably in the context of auto-immune or inflammatory disorders. The existence of immunosuppressive mechanisms supported by Tr1 lymphocytes and their IL-10 production represent an attractive hypothesis. We have previously evaluated the existence of regulatory T cells (Tr1) via high production of IL-10, in liver biopsies of three well-defined cohorts of HCV-1b infected patients. To this purpose, we compared liver biopsies of chronically infected patients including patients without liver lesions, with cirrhosis and with hepatocellular carcinoma (HCC). Using quantitative real time PCR, the results obtained demonstrate, an increased expression of interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta)_, in liver biopsies with more severe fibrosis. This observation was correlated with an increased expression during the pathogenesis progression, of the three specific markers of the Tr1 cells sub-population, recently described and confirming the Tr1 phenotype. Evidence of regulatory T cells installation in the liver of chronically infected patient and increased frequency in cirrhosis and HCC suggest a main role of these cells in the aggravation of the liver pathology. This study should bring insight of T regulatory cell implications in VHC persistence and in the pathology progression.English AbstractJournal Articleinfo:eu-repo/semantics/publishe

Live Staphylococcus aureus and bacterial soluble factors induce different transcriptional responses in human airway cells.

To characterize the response of respiratory epithelium to infection by Staphylococcus aureus (S. aureus), human airway cells were incubated for 1 to 24 h with a supernatant of a S. aureus culture (bacterial supernatant), then profiled with a pangenomic DNA microarray. Because an upregulation of many genes was noticed around 3 h, three independent approaches were then used to characterize the host response to a 3-h contact either with bacterial supernatant or with live bacteria: 1) a DNA microarray containing 4,200 sequence-verified probes, 2) a semiquantitative RT-PCR with a set of 537 pairs of validated primers, or 3) ELISA assay of IL-8, IL-6, TNFalpha, and PGE(2). Among others, Fos, Jun, and EGR-1 were upregulated by the bacterial supernatant and by live bacteria. Increased expression of bhlhb2 and Mig-6, promoter regions which harbor HIF responding elements, was explained by an increased expression of the HIF-1alpha protein. Activation of the inducible form of cyclooxygenase, COX-2, and of the interleukins IL-1, IL-6, and IL-8, as well as of the NF-kappaB pathway, was observed preferentially in cells in contact with bacterial supernatant. Early infection was characterized by an upregulation of anti-apoptotic genes and a downregulation of pro-apoptotic genes. This correlated with a necrotic, rather than apoptotic cell death. Overall, this first global description of an airway epithelial infection by S. aureus demonstrates a larger global response to bacterial supernatant (in term of altered genes and variation factors) than to exponentially growing live bacteria