OLR1 scavenger receptor knockdown affects mitotic gene expression but is dispensable for oxidized phospholipid- mediated stress signaling in SZ 95 sebocytes.

Phospholipid oxidation products (OxPL) are versatile stress signaling mediators in the skin. These lipid signaling molecules can be generated non-enzymatically or enzymatically by ultraviolet light, the major extrinsic skin aging factor. OxPL regulate cytoprotective, immunological and metabolic adaptation of the skin to oxidant stress. We here investigated whether the scavenger receptor Oxidized Low Density Lipoprotein Receptor 1 (OLR1, LOX-1) would have a function in cutaneous oxPL signaling. We found, that OLR1 is expressed in several cutaneous cell types, most prominently in cells of the sebaceous gland and in keratinocytes. We repressed OLR1 expression with siRNA in SZ95 sebocytes, exposed cells to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) and performed transcriptomic profiling. Bioinformatic analysis revealed that OxPL exposure induced the Nrf2 antioxidant stress response and aldosterone signaling. The analysis also revealed that OLR1 is not required for the transcriptional regulation induced by oxidized PAPC but interestingly, OLR1 knockdown affected expression of CNN2, HMRR, ITGB6 and KIF20A, all genes governing cell proliferation and motility. We identify sebocytes as cutaneous cells responsive to lipid mediated redox stress which is not dependent on the scavenger receptor OLR1.

No skin reactions to mineral powders in nickel-sensitive subjects.

BACKGROUND: Cosmetic products are known to be able to induce contact dermatitis. Contact dermatitis may also be induced by nickel, and it is estimated that up to 17% of women are allergic to nickel. OBJECTIVES: The aim of the present study was to investigate whether nickel sensitized individuals react to make-up products containing pigments with nickel as an impurity. PATIENTS/MATERIALS/METHODS: Twenty-three individuals with a clinical history of nickel allergy and/or with positive patch test reactions to nickel were exposed to mineral make-up products and individual pigments dispersed in alkylbenzoate (50%) in small Finn Chambers® for 48 hr. The skin reactions were evaluated visually and with a non-invasive instrument that quantifies skin erythema. RESULTS: The results showed that 74% of the included individuals showed a visible reaction to the positive control nickel sulfate, and a significant correlation was found between the visual and instrumental readings. However, none of the nickel sensitive individuals reacted to the test products. A subgroup analysis of the 50% most sensitive individuals also confirmed the absence of skin reactions to the powders. CONCLUSIONS: The bioavailability of the trace amounts of nickel in the particles was below the level needed to elicit an eczematous reaction in any of the nickel-sensitized individuals.

Recombinant human laminin-10 (alpha5beta1gamma1). Production, purification, and migration-promoting activity on vascular endothelial cells.

The laminin (LN) family of large heterotrimeric extracellular matrix glycoproteins has multiple functions: LNs take part in the regulation of processes such as cell migration, differentiation, and proliferation, in addition to contributing to the structure of basement membranes. LN-10, composed of alpha5, beta1, and gamma1 chains, is widely distributed in most basement membranes of both epithelia and endothelia. We determined the complete human cDNA sequence for the LN alpha5 chain and produced recombinant human LN-10 (rLN-10) in HEK293 cells by triple transfection of full-length cDNAs encoding the human LN alpha5, beta1, and gamma1 chains. The rLN-10 was purified using affinity chromatography and had an apparent molecular mass of approximately 800 kDa in SDS-PAGE and a native domain structure in rotary shadowing electron microscopy. By using function-blocking monoclonal antibodies, integrin alpha(3)beta(1) was found to be a major mediator of adhesion of HT-1080 and human saphenous vein endothelial cells. Human saphenous vein endothelial cells adhered more strongly to rLN-10 than to LN-1 and LN-8 and showed better migration on rLN-10, compared with several other matrices. Considering the cell adhesive and migration-promoting properties of rLN-10 on endothelial cells, this molecule could be useful in improving the biocompatibility and endothelialization of vascular grafts.