• 대한화장품학회지
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• 제46권2호
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• pp.195-204
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• 2020

본 연구에서는 피부각질형성세포에서 동의보감에 기록된 14 종의 충부약재에 대한 염증성 사이토카인 생성에 미치는 영향을 조사하였다. 이를 확인하기 위하여 멀티플렉스 사이토카인 분석으로 17 종에 대한 사이토카인을 스크리닝 하였다. 충부약재 14 종 중, 제조 및 전갈 추출물은 IL-5 생성을 억제하였고, 제조, 상표초 및 수질 추출물은 IL-6 생성을, 제조, 상표초, 지룡, 수질 및 문합 추출물은 IL-8 생성에 억제 효과를 보였다. 합개, 잠사, 선퇴 및 문합 추출물은 IL-13 생성을 억제하였으며, 귀판, 잠사 및 지룡 추출물은 MIP-1β 생성에 유의적인 효과를 확인하였다. 이러한 충부약재는 피부염증 억제를 위한 항염증제 활용 가능성에 의미를 둘 수 있지만, 그 가치를 증명하기 위해서는 피부개선을 위한 기전연구를 포함하여 인체피부모사판 모델에서 추가 실험을 통한 검증이 선행 되어야 한다.

• Nutrition Research and Practice
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• 제15권6호
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• pp.673-685
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• 2021

BACKGROUND/OBJECTIVES: Obesity is associated with the impaired regulation of T cells characterized by increased numbers of Th1 and Th17 cells and the dysregulation of vitamin D metabolism. Both obesity and vitamin D have been reported to affect autophagy; however, a limited number of studies have investigated the effects of vitamin D on T cell autophagy in obese mice. Therefore, we aimed to determine whether in vitro treatment with vitamin D affects the proliferation, function, and autophagy of T cells from obese and control mice. MATERIALS/METHODS: Five-week-old male C57BL/6 mice were fed control or high-fat diets (10% or 45% kcal fat: CON or HFDs, respectively) for 12 weeks. Purified T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies and cultured with either 10 nM 1,25(OH)₂D₃ or 0.1% ethanol (vehicle control). The proliferative response; expression of CD25, Foxp3, RORγt, and autophagy-related proteins (LC3A/B, SQSTM1/P62, BECLIN-1, ATG12); and the production of interferon (IFN)-γ, interleukin (IL)-4, IL-17A, and IL-10 by T cells were measured. RESULTS: Compared with the CON group, T cell proliferation tended to be lower, and the production of IFN-γ was higher in the HFD group. IL-17A production was reduced by 1,25(OH)2D₃ treatment in both groups. The LC3 II/I ratio was higher in the HFD group than the CON group, but P62 did not differ. We observed no effect of vitamin D treatment on T cell autophagy. CONCLUSIONS: Our findings suggest that diet-induced obesity may impair the function and inhibit autophagy of T cells, possibly leading to the dysregulation of T cell homeostasis, which may be behind the aggravation of inflammation commonly observed in obesity.

• IMMUNE NETWORK
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• 제21권6호
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• pp.43.1-43.14
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• 2021

Group 3 innate lymphoid cells (ILC3), which express IL-22 and IL-17A, has been introduced as one of pathologic cells in axial spondyloarthritis (axSpA). Dyslipidaemia should be managed in axSpA patients to reduce cardiovascular disease, and dyslipidaemia promotes inflammation. This study aimed to reveal the role of circulating ILC3 in axSpA and the impact of dyslipidaemia on axSpA pathogenesis. AxSpA patients with or without dyslipidaemia and healthy control were recruited. Peripheral blood samples were collected, and flow cytometry analysis of circulating ILC3 and CD4⁺ T cells was performed. The correlation between Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP) and circulating immune cells was evaluated. The effect of oxidized low-density lipoprotein cholesterol (oxLDL-C) on immune cell differentiation was confirmed. AxSpA human monocytes were cultured with with oxLDL-C, IL-22, or oxLDL-C plus IL-22 to evaluate osteoclastogenesis using tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative PCR of osteoclast-related gene expression. Total of 34 axSpA patients (13 with dyslipidaemia and 21 without) were included in the analysis. Circulating IL-22⁺ ILC3 and Th17 were significantly elevated in axSpA patients with dyslipidaemia (p=0.001 and p=0.034, respectively), and circulating IL-22⁺ ILC3 significantly correlated with ASDAS-CRP (Rho=0.4198 and p=0.0367). Stimulation with oxLDL-C significantly increased IL-22⁺ ILC3, NKp44^- ILC3, and Th17 cells, and these were reversed by CD36 blocking agent. IL-22 and oxLDL-C increased TRAP⁺ cells and osteoclast-related gene expression. This study suggested potential role of circulating IL-22⁺ ILC3 as biomarker in axSpA. Furthermore, dyslipidaemia augmented IL-22⁺ ILC3 differentiation, and oxLDL-C and IL-22 markedly increased osteoclastogenesis of axSpA.

• 대한한방부인과학회지
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• 제26권2호
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• pp.17-32
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• 2013

Objectives: The purpose of this study was to investigate whether Lonicera japonica(LJ) could inhibit LPS-induced type I IFN production. Methods: To evaluate inhibitory effect of LJ on type I IFN, we examined type I IFN, IRF-1, 7 and IL-10 production on LPS-induced macrophages using real time RT-PCR. Next, we observed the interaction of type I IFN, IRF-1, 7 and IL-10 using IL-10 neutralizing antibody. Finally we examined the activation of STAT-1, 3 using western blot. Results: LJ inhibited Type I IFN expression of mRNA and increased IL-10 expression of mRNA. Also LJ inhibited the level of IRF-1, 7 mRNA and the nuclear translocation of IRF-3. Further more, LJ reduced the activation of STAT-1, 3 which are involved in continuous secretion of immune cytokines. Blockade of IL-10 action caused a significant reduction of type I IFN and IRF-1, 7 than LPS-induced LJ pretreatment. Conclusions: LJ inhibits LPS-induced production of type I IFN by IL-10. This study may provide a clinical basis for anti-inflammatory properties of LJ.

• Environmental Analysis Health and Toxicology
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• 제17권4호
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• pp.325-332
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• 2002

A helper T(Th)1-mediated response is known to enhance cell -mediated immunity, while a Th2-mediated response is associated with the humoral immunity that if elevated IgE levels and eosinophilia. Prostaglandin (PG)E$_2$results in the decreased capability of Iymphocytes to produce Thl cytokines, with a shift toward a Th2 cytokine response. Chlorpyrifos (CPF) has been reported to impair the blastogenesis and response of T Iymphocytes. CPF also induces delayed febrile effects, which results from the activation of COX -PGE$_2$pathway. The purpose of this study is to determine the effort of CPF on the in vitro production of Th cytokines and the role of PGE$_2$on the CPF-induced production of Th cytokines. Splenocytes obtained from male BALB/c mice were pretreated with CPF(0.1, 1, 10 and 100$\mu$M) in the presence of absence of indomethacin or PGE$_2$for 12 h and then were incubated with concanavalin (Con) A for 48 h. These results showed that CPF remarkedly reduced the production of splenic interleukin (IL)-2 and interferon (IFN)-γ in a dose-dependent manner. CPF significantly increased the splenic IL-4 production at low doses (0.1 and 1$\mu$M) but did not affect at high doses (10 and 100 $\mu$M). Indomethacin reduced the CPF-decreased production of IL-2 and IFN-γ in a dose -dependent manner and significantly attenuated the production of IL-4 increased by CPF 0.1 $\mu$M. High dose of CPF significantly reduced the PGE$_2$-decreased production of IL-2 and IFN-γ, while the PGE$_2$- induced production of IL-4 was significantly enhanced by CPF 1 $\mu$M. These findings suggest that CPF nay down-regulate the immune response of Th 1 type by the suppressed production of IL-2 and IFN-γ, with a shift toward a Th2 cytokine response. The CPF-decreased production of Thl cytokines may not be mediated by endogenous PGE$_2$. Also, CPF may attenuate the exogenous PGE$_2$-decreased Th 1 immune response in a dose--dependent manner but may affect dose-independently the PGE$_2$-induced Th2 immune response.

• Journal of Trauma and Injury
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• 제25권1호
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• pp.17-24
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• 2012

Purpose: This study was performed to investigate whether therapeutic hypercapnia could attenuate systemic inflammatory responses in hemorrhagic shock in rats. Methods: Male Sprague-Dawley rats were mechanically ventilated and underwent pressure-controlled (mean arterial pressure: $38{\pm}1$ mmHg) hemorrhagic shock. At 10 minutes after the induction of hemorrhagic shock, the rats were divided into the normocapnia ($PaCO_2$=35-45 mmHg, n=10) and the hypercapnia ($PaCO_2$=60-70 mmHg) groups. The $PaCO_2$ concentration was adjusted by using the concentration of inhaled $CO_2$ gas. After 90 minutes of hemorrhagic shock, rats were resuscitated with shed blood for 10 minutes and were observed for 2 hours. The mean arterial pressure (MAP) and the heart rate were monitored continuously, and the results of arterial blood gas analyses, as well as the plasma concentrations of interleukin (IL)-6, IL-10, and nitrite/nitrate were compared between the normocapnia and the hypercapnia groups. Results: The MAP and the heart rate were not different between the two groups. The plasma concentration of IL-6 was significantly lower in the hypercapnia group than in the normocapnia group (p<0.05). The IL-10 concentration was not different and the IL-6 to IL-10 ratio was significantly lower in the hypercapnia group compared to the normocapnia group. The plasma nitrite/nitrate concentration of the hypercapnia group was lower than that of the normocapnia group. Conclusion: Therapeutic hypercapnia attenuates systemic inflammatory responses in hemorrhagic shock.

• 대한한의학방제학회지
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• 제18권1호
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• pp.169-179
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• 2010

The pistil of nelumbo nucifera (PNN) is used in the treatment of nocturnal pollution, hematemesis, epistaxis, metrorrhagia and diarrhoea in traditional medicine. The present study was examined to evaluate the effects of PNN on the production of pro-inflammatory mediators in vitro. After the treatment of PNN, cell viability was measured by MTT assay, nitric oxide (NO) production was monitored by measuring the nitrite content in culture medium. The protein bands were determined by immunoblot analysis and levels of cytokines were analyzed by sandwich immunoassays. In the MTT assay, the doses of PNN extract (0.03, 0.10 mg/ml) had no significant cytotoxicity. The increases of NO production and inducible nitric oxide synthase expression were detected in lipopolysaccharide(LPS)-activated Raw 264.7 cells compared with control, in contrast, these increases were significantly attenuated by pre-treatment with PNN. In cytokine assay, the massive pro-inflammatory cytokines such as tumour necrosis factor-$\alpha$, interleukin (IL)-$1{\beta}$ and IL-6 were induced in LPS-activated Raw 264.7 cells, but pre-treatment of Raw 264.7 cells with PNN caused inhibition (TNF-$\alpha$=14.17%, IL-$1{\beta}$=107.43%, IL-6=46.27%) the production of cytokines by LPS. In addition, PNN reduced prostaglandin E2 productions in a dose-dependent manner (0.03mg/ml=37.52%, 0.10 mg/ml=83.77%) as a consequence of the inhibition of cyclooxygenase-2 expression. Taken together, our data indicates that PNN can regulate the inflammatory response in macrophage cells activated by Gram-negative infection.

• Nutrition Research and Practice
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• 제7권5호
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• pp.352-358
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• 2013

Korean pine nut oil (PNO) has been reported to have favorable effects on lipid metabolism and appetite control. We investigated whether PNO consumption could influence weight gain, and whether the PNO-induced effect would result in an improvement of immune function in high-fat diet (HFD)-induced obese mice. C57BL/6 mice were fed control diets with 10% energy fat from either PNO or soybean oil (SBO), or HFDs with 45% energy fat from 10% PNO or SBO and 35% lard, 20% PNO or SBO and 25% lard, or 30% PNO or SBO and 15% lard for 12 weeks. The proliferative responses of splenocytes upon stimulation with concanavalin A (Con A) or lipopolysaccharide (LPS), Con A-stimulated production of interleukin (IL)-2 and interferon (IFN)-${\gamma}$, and LPS-stimulated production of IL-6, IL-$1{\beta}$, and prostaglandin $E_2$ ($PGE_2$) by splenocytes were determined. Consumption of HFDs containing PNO resulted in significantly less weight gain (17% less, P < 0.001), and lower weight gain was mainly due to less white adipose tissue (18% less, P = 0.001). The reduction in weight gain did not result in the overall enhancement in splenocyte proliferation. Overall, PNO consumption resulted in a higher production of IL-$1{\beta}$ (P = 0.04). Replacement of SBO with PNO had no effect on the production of IL-2, IFN-${\gamma}$, IL-6, or $PGE_2$ in mice fed with either the control diets or HFDs. In conclusion, consumption of PNO reduced weight gain in mice fed with HFD, but this effect did not result in the overall improvement in immune responses.

• Journal of Acupuncture Research
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• 제37권2호
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• pp.123-127
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• 2020

Background: This study was designed using a mouse model of atopic dermatitis [phthalic anhydride (PA)-treated mice], to investigate the anti-inflammatory effect of bee venom pharmacopuncture (BVP) in keratinocytes. Methods: Western blot analysis was performed to investigate inflammation related protein expression of iNOS, COX-2, phospho-ERK (p-ERK), and ERK, in LPS (1 ㎍/mL)-activated keratinocytes, following BVP treatment, and in PA-treated mice, after BVP treatment. Griess reaction was performed to investigate NO concentration. Enzyme-linked immunosorbent assays were used to determine the concentrations of interleukin (IL)-4+, IL-17A+, IL-13 and IL-4 in PA-treated mice after BVP treatment. In addition, monocyte, macrophage, neutrophil, and eosinophil counts were measured to observe the changes in white blood cell infiltration. Results: The keratinocytes of the BVP-treated group showed a decreased expression of iNOS, COX-2, ERK at 5 OX-2, ERK E, and p-ERK at 1, 2 and 5 RKRK ERK ERK, and a dose-dependent decrease in NO concentration at 2 and 5 ntrationof s. In the BVP-treated groups (0.1 μ.1-trea μ.1-treated gr), PA-treated mice showed recovery after 4 weeks which was dose-dependent, showing a significant decrease in clinical scores for AD, and a decreased concentration of IL-13 and IL-4 with BV treatment. There was a dose-dependent decrease in the infiltration of eosinophils, neutrophils, monocytes, macrophages, and a decreased thickness of the epidermis due to inflammation, and decreased expressions of iNOS, COX-2, p-ERK, ERK, especially in the 0.1 μ0/mL BVP-treated group, Conclusion: These results suggest that BVP may be an effective alternative treatment for atopic dermatitis.

• 동의생리병리학회지
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• 제17권3호
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• pp.711-718
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• 2003

Wanpae-tang is suggested to have antitumor activity on lung cancer. This study was performed to investigate antitumor, immune response, and apoptotic effects by Wanpae-tang in the cancer cell lines and C57BL/6 mice. Experimental studies were progressed through the anticancer activities such as, survival time, cell cytotoxicity, natural killer cell activity, productivity of interleukins and apoptotio effects. The results were summarized as follows: 1. Median survival time of Wanpae-tang treated group was prolonged to 4.1%, as compared with control group, but was not significant. 2. On the MTT assay, half-maximal inhibitory concentration(IC50) of Wanpae-tang was 15.00 ㎎/㎖ in HeLa cell, and 4.158 ㎎/㎖ in HRT-18 cell. 3. Natural killer cell activity in Wanpae-tang treated group was decreased in case of 100:1 and 10:1 effect cell/target cell ratio. 4. Production of interleukin-2, 4, 12 in Wanpae-tang treated group were significantly increased. 5. On the studies of Wanpae-tang induced apoptosis, a DNA fragmentation patterns were not appeared.