Atelocollagen is a major animal protein that is used as a highly biocompatible biomaterial. To date, atelocollagen has been used as an effective drug delivery technology to sustain the release of antitumor proteins and to enhance the antitumor activity of oligonucleotides in in vivo models. However, the biological effects of this technology are not fully understood. In the present study, we investigated the effects of atelocollagen on endothelial paracellular barrier function. An atelocollagen formulation containing oligonucleotides specifically increased the permeability of two types of endothelial cells, and the change was dependent on the molecular size, structure of the oligonucleotides used and the concentrations of the oligonucleotide and atelocollagen in the formulation. An immunohistochemical examination revealed that the formulation had effects on the cellular skeleton and intercellular structure although it did not affect the expression of adherens junction or tight junction proteins. These changes were induced through p38 MAP kinase signaling. It is important to elucidate the biological functions of atelocollagen in order to be able to exploit its drug delivery properties.
Skin sensitization resulting in allergic contact dermatitis is a common occupational health issue. In this study, the effect of mixing two skin sensitizers on the skin sensitization response was investigated. Skin sensitizers are generally classified into T helper type 1 (Th1) or T helper type 2 (Th2), depending on the induced cytokine profile. Dinitrochlorobenzene (DNCB) and oxazolone (Oxa) are Th1 skin sensitizers and phthalic anhydride (PA) and toluene diisocyanate (TDI) are Th2 skin sensitizers. We investigated the effect on skin sensitization response to mixtures of three pairs of these sensitizers: DNCB and Oxa, DNCB and PA, and PA and TDI, using guinea pig maximization test and mouse ear swelling test. In guinea pigs sensitized with the mixture of DNCB and Oxa or PA and TDI, there were changes of skin sensitization response to DNCB and Oxa, and that to PA. On the other hand, there was no mixture effect in guinea pigs sensitized with the mixture of DNCB and PA. The skin sensitization responses were decreased in mice sensitized with the mixtures of DNCB and Oxa or PA and TDI, whereas the mixture effect was not observed in mice sensitized with the mixture of DNCB and PA. The present findings revealed that mixture effect on the skin sensitization response was observed after simultaneous exposure to two skin sensitizers, and the effect was determined by combinations of mixed skin sensitizers.
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