著者

Yoshinobu Tsuruta Yushi Katsuyama Yuri Okano Toshiyuki Ozawa Satoshi Yoshimoto Hideya Ando Hitoshi Masaki Masamitsu Ichihashi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.5, pp.725-729, 2023-05-01 (Released:2023-05-01)

参考文献数

28

被引用文献数

3

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Epidermal keratinocytes protect themselves by cooperating with neighboring cells against internal and external stresses, which leads not only to the maintenance of cell homeostasis but also to the prevention of skin aging. Although it is known that nuclear factor (NF)-E2-related factor 2 (Nrf2) signaling plays a pivotal role in ameliorating oxidative stress and inflammatory responses under stress situations, it is unclear whether Nrf2 signaling in keratinocytes cooperates with neighboring cells such as dermal fibroblasts. Thus, this study was conducted to examine the influence of dermal fibroblasts on Nrf2 signaling in epidermal keratinocytes using a co-culture system. The results show that expression levels of Nrf2-regulated antioxidant factors, such as glutathione and heme oxygenase-1, in HaCaT keratinocytes (HaCaT KCs) are up-regulated in the presence of normal human dermal fibroblasts (NHDFs). In addition, the secretion of pro-inflammatory molecules, including interleukin-1α (IL-1α) and prostaglandin E2 (PGE2), is suppressed in co-cultures of NHDFs and UVB-irradiated HaCaT KCs. Interestingly, the localization of Nrf2 protein in HaCaT KCs was immediately translocated from the cytoplasm to the nucleus after the co-culture with NHDFs. These results suggest the possibility that Nrf2 signaling in keratinocytes is regulated in cooperation with dermal fibroblasts.

著者

Karin Endo Yoko Niki Yukihiro Ohashi Hitoshi Masaki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.2, pp.225-231, 2021-02-01 (Released:2021-02-01)

参考文献数

21

被引用文献数

3 4

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The dermis is mainly constructed by type I collagen fibers, which provide mechanical strength to the skin by building a frame-like structure, and by elastic fibers, which provide elasticity to respond to movements of the skin. The depletion of collagen fibers and the disappearance of oxytalan fibers, which are a type of elastic fiber, are characteristic changes in photoaged skin. Prostaglandin E2 (PGE2) is one of the chemical mediators involved in inflammation and is responsible for sunburn. Furthermore, it has been reported that PGE2 attenuates the production of collagen and the expression of elastic fiber-related factors in fibroblasts. Tranexamic acid (TXA), which is an anti-inflammatory medicine that inhibits plasmin, reduces the level of PGE2 secreted following UV exposure or after inflammatory stimulation. However, few reports have verified TXA as an anti-skin aging agent. In this study, we examined the potential of TXA as an anti-skin aging agent using repetitively UVA-irradiated fibroblasts as a model for fibroblasts located in chronically sun-exposed dermis. Repetitively UVA-irradiated fibroblasts had higher secretion levels of PGE2. In addition, fibroblasts repetitively irradiated with UVA or treated with PGE2 produced disrupted collagen and fibrillin-1 fibers. Treatment with TXA improved the formation of both types of fibers by repetitively UVA-irradiated fibroblasts by restoring the expression of fiber-related proteins at the mRNA and protein levels. Thus, these results demonstrate that TXA has potential as an anti-photoaging agent.

著者

Taeko Mizutani Ryota Mori Misaki Hirayama Yuki Sagawa Kenji Shimizu Yuri Okano Hitoshi Masaki

出版者

Japan Oil Chemists' Society

雑誌

Journal of Oleo Science (ISSN:13458957)

巻号頁・発行日

vol.65, no.12, pp.993-1001, 2016 (Released:2016-12-01)

参考文献数

35

被引用文献数

24 24

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Sodium lauryl sulfate (SLS), a representative anionic surfactant, is well-known to induce rough skin following single or multiple topical applications. The mechanism by which SLS induces rough skin is thought to result from the disruption of skin moisture function consisting of NMF and epidermal lipids. However, a recent study demonstrated that topically applied SLS easily penetrates into the living cell layers of the epidermis, which suggests that physiological alterations of keratinocytes might cause the SLS-induced rough skin. This study was conducted to clarify the effects of SLS on keratinocytes to demonstrate the contribution of SLS to the induction of rough skin. In addition, the potentials of other widely used anionic surfactants to induce rough skin were evaluated. HaCaT keratinocytes treated with SLS had increased levels of intracellular ROS and IL-1α secretion. Application of SLS on the surface of a reconstructed epidermal equivalent also showed the increased generation of ROS. Further, SLS-treated cells showed an increase of intracellular calpain activity associated with the increase of intracellular Ca2+ concentration. The increase of intracellular ROS was abolished by the addition of BAPTA-AM, a specific chelator of Ca2+. In addition, IL-1α also stimulated ROS generation by HaCaT keratinocytes. An ESR spin-labeling study demonstrated that SLS increased the fluidity of membranes of liposomes and cells. Together, those results indicate that SLS initially interacts with cell membranes, which results in the elevation of intracellular Ca2+ influx. Ca2+ stimulates the secretion of IL-1α due to the activation of calpain, and also increases ROS generation. IL-1α also stimulates ROS generation by HaCaT keratinocytes. We conclude from these results that the elevation of intracellular ROS levels is one of the causes of SLS-induced rough skin. Finally, among the other anionic surfactants tested, sodium lauryl phosphate has less potential to induce rough skin because of its lower generation of ROS.

著者

Madoka Yoshikawa Taeko Mizutani Yuri Okano Hitoshi Masaki

出版者

Japan Oil Chemists' Society

雑誌

Journal of Oleo Science (ISSN:13458957)

巻号頁・発行日

vol.69, no.7, pp.719-726, 2020 (Released:2020-07-02)

参考文献数

36

被引用文献数

2 1

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Residues of olive fruit (ROF) after the extraction of oils are an increasing source of industrial waste, because olive oil is becoming more popular as a healthy food. It has been reported that olives have some polyphenols that have an antioxidation capability. On the other hand, excess oxidative stress disrupts epidermal barrier function. This study was conducted to determine whether ROF could be utilized as an antioxidant source to reduce industrial wastes and to identify possible active materials to maintain healthy skin. Olive fruits are categorized into two groups depending on the time of harvest, young fruit (YF) and mature fruit (MF). Thus, we examined the antioxidant potentials of extracts from YF and from MF to remove reactive oxygen species (ROS) from biological and chemical aspects. HaCaT keratinocytes cultured with extracts of YF or MF had reduced levels of intracellular ROS in spite of the relatively low chemical capability against ROS scavenging. The biological effects of the YF extract were superior to those of the MF extract. The YF extract showed effective reductions of intracellular ROS and carbonylated proteins that were elevated by the stress-related hormone cortisol. In addition, the YF extract reinforced the intracellular antioxidation capability through the activation of Nrf2 signaling. Taken together, the YF extract was an effective source to reinforce the intracellular antioxidation capability. We conclude from these results that utilizing ROF would lead to the reduction of industrial wastes and would supply active materials to maintain healthy skin.

著者

Yumiko Yamawaki Taeko Mizutani Yuri Okano Hitoshi Masaki

出版者

Japan Oil Chemists' Society

雑誌

Journal of Oleo Science (ISSN:13458957)

巻号頁・発行日

vol.70, no.5, pp.647-655, 2021 (Released:2021-05-01)

参考文献数

29

被引用文献数

3

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Although extracellular carbonylated proteins (CPs) are found at higher levels in sun-exposed skin, their impact on the cellular functions of fibroblasts and their involvement in the progression of photoaging skin are not fully clarified. In our previous study, we reported that extracellular CPs increase levels of intracellular oxidative stress and result in the accumulation of newly synthesized CPs in normal human dermal fibroblasts (NHDF). Furthermore, fibroblasts exposed to CP-BSA, which is a model of extracellular CPs, had upregulated expression levels of mRNAs encoding matrix metalloproteinase-1 (MMP-1) and interleukin-8/CXCL8 (IL-8/CXCL8). These facts suggested the possibility that extracellular CPs induce a fragile structure in the dermis through the degradation of collagen and elastin. The purpose of this study was to characterize the efficacy of natural carotenoids, such as astaxanthin analogs, produced by Hematococus pluvialis (CHPs) to improve the impaired functions of fibroblasts exposed to CPs. CHPs suppressed the intracellular CP levels elevated by CP-BSA, restored mRNA expression levels of factors involved in the formation and assembly of collagen and elastin fibers and improved the formation of those fibers impaired by CP-BSA. We conclude that CHPs function as antiaging substances due to their restoration of the impaired formation of collagen and elastin fibers caused by extracellular soluble CPs.