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Biomedical subjects

Mary S Matsui

Publications and source records attributed to Mary S Matsui.

7 recordsLinked to original sources

Neuropeptide (calcitonin gene-related peptide) induction of nitric oxide in human keratinocytes in vitro.

Nitric oxide (NO) is an important signaling molecule in both the central nervous system and the periphery, where it is involved in neurotransmission, vascular and bronchial tone, inflammation, and cutaneous immune function. More recently, NO has been implicated in intracellular signaling and may have a role in cellular differentiation, cytokine expression, and apoptosis. The experiments described herein examined the effect of calcitonin gene-related protein (CGRP), a cutaneous nerve neuropeptide, on NO production in human keratinocytes in vitro. CGRP stimulated two distinct increases in NO production: one within 30 minutes and a second at 24 hours. CGRP stimulated a modest increase in inducible nitric oxide synthase (iNOS) at 3-6 hours. Experimental evidence suggested that CGRP stimulated both constitutive NOS activity and generation of NO via nitrosothiol degradation within the first hour. Production of NO was paralleled by a decrease in nitrosothiol levels for 2 hour, suggesting that immediate NO release may originate from pre-existing stores. Nitrosothiols are ubiquitous molecules that comprise an important NO pool and have intracellular regulatory roles, particularly linked to oxidative stress. The present data indicate that, in addition to its known cAMP signaling pathway, CGRP may act to regulate keratinocyte biology through intracellular NO by modulation of S-nitrosothiol stores and stimulation of NOS activity.

Calcitonin Gene-Related Peptide↗

UV radiation-induced immunosuppression and skin cancer.

UV radiation (UVR)-induced skin cancers in mice are highly antigenic and rejected by the host immune system when transplanted to syngeneic recipients. Exposure to UVB radiation causes immunologic changes that inhibit the host immune system from recognizing the tumor and leads to immunologic tolerance. This tolerance involves the appearance of regulatory T cells within the tumor-bearing hosts, which inhibit immunologic recognition of the tumor. Experiments performed with chemical haptens as surrogates for tumor antigens indicate that this comes about because of abnormal antigen presentation. Antigen-presenting cells (APCs) are prevented from performing their normal function by cytokines, most notably interleukin 10 (IL-10) and tumor necrosis factor alpha (TNF-alpha), released by keratinocytes and mast cells. Release of cytokines results from a cascade of UVR-induced events involving neuropeptides. Other immunosuppressive mediators released in the skin, as well as direct damage to Langerhans cells (LCs), are suspected of playing a role in UVR-induced immunosuppression. As a whole, data suggest a role for the immunologic effects of UVR in the pathogenesis of skin cancer.

Animals↗

Impact of stress of marital dissolution on skin barrier recovery: tape stripping and measurement of trans-epidermal water loss (TEWL).

BACKGROUND: Psychological stress of marital disruption is associated with significant increases in a variety of psychological and physical disorders. The effect of stress on the immune system is well documented and skin disorders have been reported to exacerbate during stressful situations. This study was designed to observe the effects of stress on skin barrier strength and recovery. Twenty-eight healthy females age 21-45 who were in the process of marital separation were tested for skin barrier strength and recovery. The panel was chosen on the basis of the intensity of self perceived stress. The control group was an age-matched group of self perceived 'happy' subjects. Servomed evaporimeter was used to measure trans-epidermal water loss (TEWL) from cheek area of the face, before and after removing stratum corneum layers with tape strippings. Skin barrier strength was defined as the number of tape strippings required to disrupt skin barrier, which is a TEWL of 18 g/m2/h or more. Barrier recovery was denoted by the level of TEWL, 3 h and 24 h after barrier disruption. RESULTS: There was no correlation between the degree of stress and barrier strength. However, individuals with high stress recovered slower than the individuals with low stress after 3 h (R = 0.64) and 24 h (R = 0.74). CONCLUSIONS: Psychological stress of marital dissolution does not appear to change skin barrier strength but has a negative impact on skin barrier recovery.

Adult↗

Sulfated polysaccharides from red microalgae have antiinflammatory properties in vitro and in vivo.

The primary goal of the present research was to determine whether sulfated polysaccharides derived from red microalgae possess antiinflammatory properties when directed against specific parameters of human skin inflammation. These unique biopolymers were studied in both in vitro and in vivo models of skin inflammation. Human subjects were recruited to participate in a study in which the polysaccharide material was applied topically and shown to inhibit cutaneous erythema induced by a known irritant. Leukocyte migration from capillary blood into sites of inflammation is an essential component of the inflammatory process and occurs in a series of steps, two of which are adhesion and chemotaxis. In vitro, the polysaccharide material primarily inhibited the migration of polymorphonuclear leukocytes (PMNs) toward a standard chemoattractant molecule and also partially blocked adhesion of PMNs to endothelial cells. The data obtained strongly suggest that sulfated polysaccharides derived from red microalgae have significant beneficial potential for use in topical products. In addition, the data suggested that the antiinflammatory mechanism for the polysaccharide was, at least in part, due to inhibition of circulating immune cell recruitment toward inflammatory stimuli.

Administration, Topical↗

Implications of UV-induced inflammation and immunomodulation.

Sunscreens are the most effective and widely available interventions for sun damage, other than sun avoidance or clothing. However, sun-screens vary widely in their ability to screen various UV wavelength components. Testing methods for sunscreens rely on UV-induced erythema to determine a sun protection factor (SPF), primarily a measure of UVB protection only. Determination of an immune protection factor (IPF) has been proposed as an alternative or adjunctive measure to SPF, and, indeed, recent studies show that the IPF can detect the added in vivo functionality of sunscreens--such as high levels of UVA protection--that the SPF cannot. Consensus on the definition of IPF, however, is required. Data are available on quantification of the IPF for restoring the afferent or induction arm of contact sensitivity, but other immune parameters also have been measured. A review of in vivo studies in humans, in which sunscreens are used to intervene in UV-induced modulation of immune response, cells, or cytokines, highlights the technical variables and statistical approaches that must be standardized in the context of an IPF for regulatory product claim purposes. Development of such IPF standards would allow the integration of both UVB and non-UVB solar wave-band effect-reversals. In addition, it could be applied to integrate the effects of other ingredients with protective function (ie, antioxidants, retinoids, or other novel products) and spur the development of more advanced and complete protection products.

Humans↗

Pomegranate fruit extract modulates UV-B-mediated phosphorylation of mitogen-activated protein kinases and activation of nuclear factor kappa B in normal human epidermal keratinocytes paragraph sign.

Excessive exposure of solar ultraviolet (UV) radiation, particularly its UV-B component, to humans causes many adverse effects that include erythema, hyperplasia, hyperpigmentation, immunosuppression, photoaging and skin cancer. In recent years, there is increasing use of botanical agents in skin care products. Pomegranate derived from the tree Punica granatum contains anthocyanins (such as delphinidin, cyanidin and pelargonidin) and hydrolyzable tannins (such as punicalin, pedunculagin, punicalagin, gallagic and ellagic acid esters of glucose) and possesses strong antioxidant and anti-inflammatory properties. Recently, we have shown that pomegranate fruit extract (PFE) possesses antitumor promoting effects in a mouse model of chemical carcinogenesis. To begin to establish the effect of PFE for humans in this study, we determined its effect on UV-B-induced adverse effects in normal human epidermal keratinocytes (NHEK). We first assessed the effect of PFE on UV-B-mediated phosphorylation of mitogen-activated protein kinases (MAPK) pathway in NHEK. Immunoblot analysis demonstrated that the treatment of NHEK with PFE (10-40 microg/mL) for 24 h before UV-B (40 mJ/cm(2)) exposure dose dependently inhibited UV-B-mediated phosphorylation of ERKl/2, JNK1/2 and p38 protein. We also observed that PFE (20 microg/mL) inhibited UV-B-mediated phosphorylation of MAPK in a time-dependent manner. Furthermore, in dose- and time-dependent studies, we evaluated the effect of PFE on UV-B-mediated activation of nuclear factor kappa B (NF-kappaB) pathway. Using Western blot analysis, we found that PFE treatment of NHEK resulted in a dose- and time-dependent inhibition of UV-B-mediated degradation and phosphorylation of IkappaBalpha and activation of IKKalpha. Using immunoblot analysis, enzyme-linked immunosorbent assay and electrophoretic mobility shift assay, we found that PFE treatment to NHEK resulted in a dose- and time-dependent inhibition of UV-B-mediated nuclear translocation and phosphorylation of NF-kappaB/p65 at Ser(536). Taken together, our data shows that PFE protects against the adverse effects of UV-B radiation by inhibiting UV-B-induced modulations of NF-kappaB and MAPK pathways and provides a molecular basis for the photochemopreventive effects of PFE.

Cells, Cultured↗