• BMB Reports
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• v.50 no.11
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• pp.584-589
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• 2017

Intercellular adhesion molecule-1 (ICAM-1), which is induced by tumor necrosis factor (TNF)-${\alpha}$, contributes to the entry of immune cells into the site of inflammation in the skin. Here, we show that protein tyrosine phosphatase non-receptor type 21 (PTPN21) negatively regulates ICAM-1 expression in human keratinocytes. PTPN21 expression was transiently induced after stimulation with TNF-${\alpha}$. When overexpressed, PTPN21 inhibited the expression of ICAM-1 in HaCaT cells but PTPN21 C1108S, a phosphatase activity-inactive mutant, failed to inhibit ICAM-1 expression. Nuclear factor-${\kappa}B$ (NF-${\kappa}B$), a key transcription factor of ICAM-1 gene expression, was inhibited by PTPN21, but not by PTPN21 C1108S. PTPN21 directly dephosphorylated phospho-inhibitor of ${\kappa}B$ ($I{\kappa}B$)-kinase ${\beta}$ ($IKK{\beta}$) at Ser177/181. This dephosphorylation led to the stabilization of $I{\kappa}B{\alpha}$ and inhibition of NF-${\kappa}B$ activity. Taken together, our results suggest that PTPN21 could be a valuable molecular target for regulation of inflammation in the skin by dephosphorylating p-$IKK{\beta}$ and inhibiting NF-${\kappa}B$ signaling.

• The Journal of the Korean Society for Microbiology
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• v.21 no.3
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• pp.311-329
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• 1986

The experimental exposure of animals to sources of ultraviolet radiation (UVR) which emit their energy primarily in the UVB region (280-320nm) is known to result in a number of well-described changes in the recipient's immune competence. Two such changes include a depressed capacity to effectively respond immunologically to transplants of syngeneic UVR tumors and a markedly reduced responsiveness to known inducers of delayedtype (DTH) and contact hypersensitivity (CH) reactions. The results of experiments that were designed to elucidate the mechanisms responsible for UVR-induced immunomodulation have implicated: 1) an altered pattern of lymphocyte recirculation, 2) suppressor T cells(Ts), 3) deviations in systemic antigen presenting cell (APC) potential. 4) changes in the production of interleukin-1-like molecules, and 5) the functional inactivation of epidermal Langerhans cells in this process. The exposure of skin to UVR, therefore, causes a number of both local and systemic alterations to the normal host immune system. In spite of this seeming complexity and diversity of responses, our recent studies have established that each of the UVR-mediated changes is probably of equal importance to creating the UVR-induced immunocompromised state. Normal animals were exposed to low dose UVR radiation on their dorsal surfaces under conditions where a $3.0\;cm^2$ area of skin was physically protected from the light energy. Contact sensitization of these animals with DNFB, to either the irradiated or protected back skin, resulted in markedly reduced CH responses. This was observed in spite of a normal responsiveness following the skin sensitization to ventral surfaces of the UVR-exposed animals. Systemic treatment of the low dose UVR recipients with the drug indomethacin (1-3 micrograms/day) during the UVR exposures resulted in a complete reversal of the depressions observed following DNFB sensitization to "protected" dorsal skin while the altered responsiveness found in the group exposed to the skin reactive chemical through directly UVR-exposed sites was maintained. These studies implicate the importance of EC as effective APC in the skin and also suggest that some of the systemic influences caused by UVR exposure involve the production of prostaglandins. This concept was further supported by finding that indomethacin treatment was also capable of totally reversing the systemic depressions in CH responsiveness caused by high dose UVR exposure (30K joules/$m^2$) of mice. Attempts to analyze the cellular mechanisms responsible established that the spleens of all animals which demonstrated altered CH responses, regardless of whether sensitization was through a normal or an irradiated skin site, contained suppressor cells. Interestingly, we also found normal levels of T effector cells in the peripheral lymph nodes of the UVR-exposed mice that were contact sensitized through normal skin. No effector cells were found when skin sensitization took place through irradiated skin sites. In spite of such an apparent paradox, insight into the probable mechanisms responsible for these observations was provided by establishing that UVR exposure of skin results in a striking and dose-dependent blockade of the efferent lymphatic vessels in all peripheral lymph nodes. Therefore, the afferent phases of immune responses can apparently take place normally in UVR exposed animals when antigen is applied to normal skin. The final effector responses, however, appear to be inhibited in the UVR-exposed animals by an apparent block of effector cell mobility. This contrasts with findings in the normal animals. Following contact sensitization, normal animals were also found to simultaneously contain both antigen specific suppressor T cells and lymph node effector cells. However, these normal animals were fully capable of mobilizing their effector cells into the systemic circulation, thereby allowing a localization of these cells to peripheral sites of antigen challenge. Our results suggest that UVR is probably not a significant inducer of suppressor T-cell activity to topically applied antigens. Rather, UVR exposure appears to modify the normal relationship which exists between effector and regulatory immune responses in vivo. It does so by either causing a direct reduction in the skin's APC function, a situation which results in an absence of effector cell generation to antigens applied to UVR-exposed skin sites, inhibiting the capacity of effector cells to gain access to skin sites of antigen challenge or by sequestering the lymphocytes with effector cell potential into the draining peripheral lymph nodes. Each of these situations result in a similar effect on the UVR-exposed host, that being a reduced capacity to elicit a CH response. We hypothesize that altered DTH responses, altered alloresponses, and altered graft-versus-host responses, all of which have been observed in UVR exposed animals, may result from similar mechanisms.

• Journal of Haehwa Medicine
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• v.19 no.2
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• pp.65-83
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• 2011

Various related factors and tissue changes in vitro and in vivo were observed to investigate the efficacy of HYBH on atopic dermatitis. The results are described below. HYBH improved the atopic dermatitis symptoms by naked eye examination, and significantly decreased dermatitis clinical index at 14 weeks. HYBH significantly decreased CD4+/CD45+, CD4+, CD8+, CD3+/CD69+ immune cell ratios in PBMC by 28%, 16%, 30%, 26% and 22% respectively. HYBH significantly decreased CD11b+/Gr-1+, CD3 immune cell ratios in dorsal skin by 35.3% and 67.5% respectively. HYBH significantly decreased the expression of IL-4 and IFN-${\gamma}$ in spleen by 23% and 15% respectively. HYBH significantly decreased the production rate of IL-5, IL-13 and histamine in serum by 17%, 23%, and 8.8% respectively and increased IL-17 production by 17%. HYBH significantly decreased immunoglubulins IgG1 and IgE production in serum. The results above indicated that treatment of HYBH improved atopic dermatitis symptoms by anti-oxidant activity and immune modulation activity as a clinical evidence. Also, different fermentation conditions using various microbial strains should be accumulated as the clinical evidence for broad application in the future.

• IMMUNE NETWORK
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• v.3 no.4
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• pp.302-309
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• 2003

Background: CTLA4 (CD152), which is expressed on the surface of T cells following activation, has a much higher affinity for B7 molecules comparing to CD28, and is a negative regulator of T cell activation. In contrast to stimulating and agonistic capabilities of monoclonal antibodies specific to CTLA-4, CTLA4Ig fusion protein appears to act as CD28 antagonist and inhibits in vitro and in vivo T cell priming in variety of immunological conditions. We've set out to confirm whether inhibition of the CD28-B7 costimulatory response using a soluble form of human CTLA4Ig fusion protein would lead to persistent inhibition of alloreactive T cell activation. Methods: We have used CHO-$dhfr^-$ cell-line to produce CTLA4Ig fusion protein. After serum free culture of transfected cell line we purified this recombinant molecule by using protein A column. To confirm characterization of fusion protein, we carried out a series of Western blot, SDS-PAGE and silver staining analyses. We have also investigated the efficacy of CTLA4Ig in vitro such as mixed lymphocyte reaction (MLR) & cytotoxic T lymphocyte (CTL) response and in vivo such as experimental autoimmune encephalomyelitis (EAE), graft versus host disease (GVHD) and skin-graft whether this fusion protein could inhibit alloreactive T cell activation and lead to immunosuppression of activated T cell. Results: In vitro assay, CTLA4Ig fusion protein inhibited immune response in T cell-specific manner: 1) Human CTLA4Ig inhibited allogeneic stimulation in murine MLR; 2) CTLA4Ig prevented the specific killing activity of CTL. In vivo assay, human CTLA4Ig revealed the capacities to induce alloantigen-specific hyporesponsiveness in mouse model: 1) GVHD was efficiently blocked by dose-dependent manner; 2) Clinical score of EAE was significantly decreased compared to nomal control; 3) The time of skin-graft rejection was not different between CTLA4Ig treated and control group. Conclusion: Human CTLA4Ig suppress the T cell-mediated immune response and efficiently inhibit the EAE, GVHD in mouse model. The mechanism of T cell suppression by human CTLA4Ig fusion protein may be originated from the suppression of activity of cytotoxic T cell. Human CTLA4Ig could not suppress the rejection in mouse skin-graft, this finding suggests that other mechanism except the suppression of cytotoxic T cell may exist on the suppression of graft rejection.

• Journal of fish pathology
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• v.21 no.3
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• pp.219-228
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• 2008

The effects of dietary yeast β-glucan administration on growth, nonspecific immune responses, serum lysozyme, skin mucous lysozyme, NBT (nitroblue tetrazolium) reduction by phagocytes, and disease resistance against Edwardsiella tarda in Japanese eel, Anguilla japonica were evaluated. Fish were fed the diets supplemented with 0%, 0.1% and 0.5% of yeast β-glucan to a commercial diet for 6 weeks. The body weight gain from the fish fed on the 0.5% supplemented diet for 6 weeks was significantly higher than the control. Both serum and skin mucous lysozyme were significantly higher in the all experimental groups except 2 weeks of 0.5% group. The bactericidal activity of serum was slightly increased at 6 weeks. Also, The intracellular superoxide anion production of kidney phagocytes was significantly higher in the all experimental groups. The diet supplemented with 0.1% were also found to raise the relative percent survival (RPS) of Japanese eel after an artificial challenge with 1×107 cells of Edwardsiella tarda per fish. The results suggested the potential of yeast β-glucan to activate some innate immune responses and to improve the growth in Japanese eel.

• Journal of Advanced Information Technology and Convergence
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• v.10 no.2
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• pp.199-214
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• 2020

An important technique of the present invention is primarily to parallel light detection, self-pulse therapy after diagnosis. Herpes zoster is a disease caused by varicella zoster virus, and the virus that has been latent in the dorsal root ganglion that controls the skin segment loses its immune system and physically damages it. It is an acute skin disease in which acute pain and bullous rash occur along the sensory ganglia, which are rehab by inducers such as malignant tumors. Dorsal root ganglion after complete recovery of varicella, relapsed after incubation in brain ganglion, latent virus sometimes suppressed activity by cell mediated immunity, and in cell ganglion with reduced cellular immunity. It proliferates and destroys neurons, causing pain while forming a rash and blisters. This can reduce cell necrosis and increase the phagocytosis and enzymatic activity through the movement of ions through the cell membrane, depolarization and membrane potential change, growth factor secretion, calcium ion transfer, chondrocyte synthesis, etc., And may offer treatment options for lesions of herpes zoster and post-herpetic neuralgia (PHN).Therefore, according to the present research, the diagnosis and treatment device of treating paing for herpes zoster and post-herpetic pain can be implemented in the early stage of herpes zoster, and conventional analgesic regulation, anti-inflammatory effect, post-herpetic neuralgia.

• Journal of the Korea Convergence Society
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• v.12 no.8
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• pp.309-315
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• 2021

Pycnogenol extracted from pine bark is a component with great antibacterial activity and antioxidant effect. It is applied as a natural anti-inflammatory agent with various medical effects including anti-inflammatory effects, regulation of blood pressure, regulation of the immune system, and inhibition of cancer cell growth. However, research related to cosmetics is limited. Therefore, in this study, the effect of Pycnogenol on the skin was studied through a clinical approach. Changes in skin condition were observed after using cosmetics with Pycnogenol and without Pycnogenol for 6 weeks for 10 clinicians in each group. We observed the effect of pore reduction, wrinkle reduction around eyes, a decrease of the number and angle of loose pores, and reduction of pigmentation. Therefore, cosmetics containing Pycnogenol have the effect of improving skin problems of aging skin.

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.10
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• pp.1496-1501
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• 2002

A $2{\times}3$ factorial arrangement of treatments was used in a completely randomized design to determine the effects of dietary Zn on performance and immune response of acutely endotoxemic growing pigs (n=96, mean BW=24.9 kg). Factors included 1) intramuscular injection of $10{\mu}g/kg$ BW of Escherichia coli lipopolysaccharide (LPS) or control and 2) supplemental Zn at 10, 50, or 150 ppm. Diets were fed beginning after weaning (initial body weight=7.6 kg) in the nursery and continued for 16 d into the grower phase. The basal corn-soybean meal grower diet contained 1% lysine and 34.3 ppm Zn. Pigs were acclimated for 12 d in the growerfinishing facility before LPS treatment on d 13. Gain, feed intake, and feed efficiency were unaffected by dietary Zn. Feed intake decreased (p<0.10) and gain/feed was greater (p<0.10) from d 13 to d 16 for pigs injected with LPS. Serum Zn and alkaline phosphatase activity increased (p<0.05) with increasing Zn levels. The febrile response to LPS peaked at 6 h post exposure and pigs were afebrile within 12 h. Rectal temperature was greater (p<0.05) in pigs receiving 50 and 150 ppm Zn than in pigs supplemented with 10 ppm Zn. In vivo cellular immune response, measured on d 13 by skin thickness response to phytohemagglutinin (PHA), was greater after 6 h (p<0.05) in pigs fed 10 ppm Zn and exposed to LPS compared to all other treatments, but was not affected at 12, 24 or 48 h. Zinc did not affect mitogen induced lymphocyte proliferation. Zinc supplemented at 50 or 150 ppm resulted in an enhanced febrile response in pigs subjected to iatrogenic endotoxemia, but did not affect pig performance or immune response measurements.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.1
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• pp.135-142
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• 2015

This study was conducted to evaluate the effect of inclusion of propolis extraction residue in the feed of broilers from 1 to 21 d of age on phagocytic activity of macrophages, cutaneous basophil hypersensitivity response to phytohemagglutinin, antibody production against Newcastle disease, lymphoid organ weight and hematological profile and to determine the optimal level of inclusion. 120 chicks, reared in metabolism cages until 21 days of age, were distributed in a completely randomized design, with five treatments (0%, 1%, 2%, 3%, and 4% of propolis residue) and six replications. The relative weight of thymus and monocyte percentage were affected by propolis residue, with a quadratic response (p<0.05) and lowest values estimated at 2.38% and 2.49%, respectively. Changes in relative weight of cloacal bursa and spleen, percentage of lymphocyte, heterophil, basophil, eosinophil, and heterophil:lymphocyte ratio, antibody production against Newcastle disease, phagocytic activity of macrophages and the average number of phagocytosed erythrocytes were not observed. The nitric oxide production with regard to positive control (macrophages+erythrocytes) decreased linearly (p<0.05) with increased doses of propolis residue. The remaining variables of nitric oxide production (negative control - macrophages, and difference between the controls) were not affected by propolis residue. The cutaneous basophil hypersensitivity response to phytohemagglutinin as determined by the increase in interdigital skin thickness exhibited a quadratic response (p<0.05), which predicted a lower reaction response at a dose of 2.60% of propolis residue and highest reaction response after 43.05 hours of phytohemagglutinin injection. The inclusion of 1% to 4% of propolis extraction residue in broiler diets from 1 to 21 days of age was not able to improve the immune parameters, despite the modest changes in the relative weight in thymus, blood monocyte percentage, nitric oxide concentration, and interdigital reaction to phytohemagglutinin.

• The Korea Journal of Herbology
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• v.30 no.5
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• pp.23-28
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• 2015

Objectives : The aim of this study is to investigate cell viability, anti-inflammatory, antioxidant, immunoenhancing activity using various extracts of Yeonsan Ogye.Methods : In order to evaluate cytotoxicity, MTT assay was performed. We investigated production levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-αand interleukin (IL)-6, and nitric oxide(NO) in LPS-induced RAW 264.7 cells. NO production in RAW 264.7 cells was measured by using Griess reagent. Cytokines including IL-6 and TNF-αwere measured by Luminex and ROS was measured by Flow cytometry.Results : No cytotoxicity of various extracts of Yeonsan Ogye was observed in RAW 264.7 cells. Productions of ROS in RAW 264.7 cells were increased from extraction of bones and decreased from extraction of skin. Also, productions of NO in RAW 264.7 cells were increased to bone extract and decreased at skin extract. In addition, productions of pro-inflammatory cytokines (IL-6 and TNF-α) in LPS-induced RAW 264.7 cells were decreased at skin, meat extracts, respectively. Finally, the levels of immune-related cytokines (IL-6 and TNF-α) were increased compared to those of the normal group.Conclusions : It is concluded that Yeonsan Ogye extracts seem to have significant biological activities likes anti-inflammatory, antioxidant, immuno-enhancing etc. These results may be developed as a raw material for new health food and new therapeutics to ease the symptoms related with inflammatory and oxidative stress. In terms of oriental traditional medicine, we expect that it contribute to building of EBM (Evidence-Based Medicine) from the this result.