Cyclosporine A(CsA) is a widely used immunosuppressant for transplant patients and is also used for the treatment of a wide variety of systemic diseases with immunologic disorders. However, its use is frequently limited because of complications such as nephrotoxicity or gingival hyperplasia. Although several hypotheses have been postulated for CsA-induced gingival hyperplasia, i.e. various cytokine effects of inflammatory cells, existence of plaque or CsA itself, but its pathogenesis is still unclear. For experimental chronic CsA toxicity, salt depletion has been shown to increased susceptibility of rodents to the effects of CsA, and this maneuver facilitates production of arteriolopathy and interstitial fibrosis in kidney that mimic the changes found in human. The purpose of this study was to evaluate pathogenesis of CsA-induced gingival hyperplasia by comparing changes between CsA administration groups of normal standard diet and those of low salt diet group. Specific pathogen-free, 20 to 25 days old(120 to 150 g), male Fisher-344 rats(KIST, Korea), 120 to 150g of body weight, were assigned to four groups of six animals each after one week of adaptation period for powder food. Group 1 received olive oil($300{\mu}l/g\;of\;diet$) with normal standard diet(0.4% of sodium)(NSD). Group 2 received CsA(Cypol-N, Jonggundang, Korea; $300{\mu}g/g\;of\;diet$) with normal standard diet(NSD+CsA). Group 3 received same amount of olive oil with low salt diet(0.05 % of sodium, Teklad Premier, U.S.A.)(LSD). Group 4 received same dose of CsA with low salt diet(LSD+CsA). Rats were pair fed and were sacrificed after six weeks. Renal histologic lesions associated with CsA, consisted of cortical interstitial fibrosis, tubular atrophy and hyalinization of arterioles and the impairment of renal function including increase of serum creatinine and decrease of glomerular filtration rate was more severe in low salt diet group. These were proved as the results of activated of renin-angiotensin system in the kidney by low salt condition. Meanwhile the degree of gingival hyperplasia at incisor and molar tooth was less severe in low salt diet group compared with normal sodium diet group. Hyperplastic gingiva showed mild epithelial hyperplasia and expanded underlyng stroma which consisted of matrix increasement, capillary proliferation and dilatation. While the number and the activation of fibroblasts were increased, inflammatory cells were rare in the stroma. The immunohistochemistry for TGF-${\beta}_1$ in the kidney and gingiva revealed stronger positive in LSD+CsA in kidney but in gingiva of NSD+CsA. These results suggested followings; Gingival hyperplasia can be developed without inflammatory cells infiltration and seemed not induced by CsA by itself. The major role for gingival hyperplasia by CsA would be the secondary effect of TGF-${\beta}$, which maybe upregulated by CsA administration. Low salt diet can attenuate this hyperplasia perhaps by decreasing the activation of $TGF-{\beta}$.
Leptin is an adipocyte-secreted hormone and its plasma levels correlate with total body fat mass, however, it also plays a regulatory role in immunity, inflammation, and hematopoiesis. Chemokine is known as a chemoattractant cytokine in inflammatory reaction, but its role in leptin reaction has not been well studied. In this study, the direct effect of leptin on the expression of chemokine mRNAs and lipopolysaccharide (LPS)-induced chemokine KC mRNA in mouse peritoneal macrophages was investigated. Leptin did not induce the expression of lymphotactin, RANTES, eotaxin, MIP-1$\beta$, MIP-1$\alpha$, MIP-2, MCP-1, IP-10, TCA-3, and KC mRNA in mouse peritoneal macrophages, and had no direct effect on the expression of these LPS-induced chemokine mRNAs except KC mRNA. The synergistic effect of leptin on the expression of LPS-induced KC mRNA occurred late in the time course of response to LPS. The increased expressions of Ob-Rb mRNA and leptin receptor protein were detected during the LPS treatment. Leptin produced a substantial increase in the stability of the LPS-induced KC mRNA, and the synergistic effect of leptin on LPS-induced KC mRNA expression was further augmented by cycloheximide (CHX). Pyrrolidine dithiocarbamate (PDTC) did not block the synergistic effect of leptin on LPS-induced KC mRNA expression in mouse peritoneal macrophages. These data suggest that although leptin has no direct effect on the expression of lymphotactin, RANTES, eotaxin, MIP-1$\beta$, MIP-1$\alpha$, MIP-2, MCP-1, IP-10, TCA-3, and KC mRNA in mouse peritoneal macrophages, the synergistic effect of leptin on the expression of LPS-induced KC mRNA has the possibility that LPS might induce the expression of the Ob-Rb receptor or an unknown gene(s) that sensitizes macrophages to the synergistic function of leptin. Therefore, further studies are necessary to examine leptin as a regulatory factor of chemokine production.
Yang, Su Jin;Lee, Si Young;Lee, Hannah;Park, Yeong Chul;Choi, Seon Kang;Yu, Chang Yeon;Chung, Ill Min;Lim, Jung Dae
Korean Journal of Medicinal Crop Science
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v.24
no.5
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pp.408-419
/
2016
Background: In recent years, adjuvants have received increasing attention owing to the development of purified subunit and synthetic vaccines which are poor immunogens and require additional adjuvants to evoke an immune response. Therefore, immunologic adjuvants have been developed and tested. Plant polysaccharides have been recognized as effective biological response modifiers with low toxicity. Methods and Results: In this study, the polysaccharide from the aboveground part of Astragalus membranaceus Bunge containing immunomodulating arabino-3,6-galactan was evaluated for its hemolytic activity and adjuvant potential in the specific cellular and humoral immune responses to ovalbumin. The polysaccharide from the aboveground part of Astragalus membranaceus Bunge was co-immunized with the purified Vi capsular polysaccharide of Salmonella typhi vaccine in mice. The polysaccharide from the aboveground part of Astragalus membranaceus Bunge did not induce any hemolytic activity or side effects at doses up to $500{\mu}g/m{\ell}$. The concanavalin A-, lipopolysaccharide-, and ovalbumin-induced splenocyte proliferation and serum ovalbumin-specific IgG, IgG1 and IgG2b antibody titers in immunized mice were significantly enhanced by AMA. Pharmacological data revealed that the polysaccharide from the aboveground part of Astragalus membranaceus Bunge increased antigen-specific antibody levels in immunized mice. The polysaccharide from the aboveground part of Astragalus membranaceus Bunge-adjuvanted purified Vi capsular polysaccharide of Salmonella typhi vaccine improved the proliferation of splenocytes and macrophages as well as stimulated cytokine production. Conclusions: These results suggest that the polysaccharide from the aboveground part of Astragalus membranaceus Bunge-adjuvanted vaccines enhanced humoral and cellular immunity and that the polysaccharide from the aboveground part of Astragalus membranaceus Bunge is a safe and efficacious adjuvant candidate suitable for use in prophylactic and therapeutic vaccines.
The anti-inflammatory activity of onion juices prepared from sulfur-fertilized onions was investigated by measuring the secretion of proinflammatory cytokines from human monocytes cultured under hyperglycemic condition. Human monocytic (THP-1) cells were cultured under normoglycemic (NG, 5.5 mM glucose) or hyperglycemic (HG, 25 mM glucose) conditions, with or without onion juice. Without onion juice, cell viability decreased significantly in the HG state for 48 h, compared to that in the NG state. With onion juice ($50-150{\mu}L$) treatment, the cell viability was not different from that under the NG condition, suggesting that onion juice prevented HG-induced monocytes cytotoxicity. While the HG condition in vitro significantly induced TNF-${\alpha}$ release from THP-1 cells and its gene expression, onion juice ($50{\mu}L$) significantly suppressed them. This indicates that onion juice inhibited HG-induced cytokine production in monocytes. These results suggest that onion juice from sulfur-fertilized onions can be used for the prevention of diabetes and related diseases.
KH-red ginseng/chlorella (KH-RG/C) is the mixed material of the Korean red ginseng powder (Panax ginseng, 75%) and extract of Chlorella vulgaris (25%). To evaluate the effects of KH-RG/C on endurance capacity and immune regulation, the forced swimming test (FST) was conducted. The immobility time in the FST was significantly decreased in KH-RG/C treated group compared with the DW-treated group at the 3 and 10 days, respectively. In the analysis of the blood biochemical parameters, KH-RG/C treatment significantly increased the glucose level. However, the lactic dehydrogenase level decreased. Although KH-RG/C increased aspartate aminotransferase, it was not different significantly. And KH-RG/C had no affects in the alanine aminotransferase, and blood urea nitrogen levels. In splenocytes and macrophages, KH-RG/C also did not affect the interleukin (IL)-2, IL-4, and IL-12 production. These results suggest that KH-RG/C may influence to immune regulation through increasing the physical endurance capacity without effect in activation of immune cells.
Kim, Hyang Suk;Chung, Kyung Tae;Lee, In Hwan;Choi, Woo Bong;Lee, Jong Hwan;Hyun, Sook Kyung;Kim, Byung Woo;Hwang, Hye Jin
Journal of Life Science
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v.24
no.1
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pp.61-66
/
2014
The purpose of this study was to investigate the immunomodulatory effects of Alpina officinarum (AO) ethanol extract on immunocompromised mice. The mice were injected intraperitoneally with an immunosuppressive drug, cyclophosphamide, and then administrated orally with 30, 100, and 300 mg/kg of ethanol extract of AO (AO 30, AO 100, and AO 300, respectively). The concentrations of cytokines and immunoglobulins (IgM, IgA, IgG) in serum were measured. The body weight of the mice and spleen cell number of the AO-fed group showed no significant difference compared to a control group. The concentrations of several cytokines, including IL-2, IFN-${\gamma}$, and TGF-${\beta}$, in serum showed a significant increase in the AO 100 group compared to the control and other groups (p<0.05). The IL-4 level showed no significant difference in the experimental groups. The supplementation of AO (30, 100, 300 mg/kg) significantly increased the concentration of IgM (p<0.05). The concentration of IgA was significantly increased in the AO 100 group (p<0.05) compared to the control group. It can be concluded that AO ethanol extract enhances immune function by promoting the production of cytokines and immunoglobulins.
The objective of this study was to evaluate the anti-inflammation effect of extract of Carthamus tinctorious seed, on skin obtained from Gyeong buk, Korea. Regulatory mechanisms of cytokines and nitric oxide (NO) involved in immunological activity of Raw 264.7 cells. Tested cells were pretreated with 70% ethanol extracted of Carthamus tinctorious seed and further cultured for an appropriated time after the addition of lipopolyssacharide (LPS). During the entire experimental period, 5, 10, 25 and 50 ${\mu}g/ml$ of Carthamus tinctorious seed showed no cytotoxicity. In these concentrations, ethyl acetate layer of ethanol extracted Carthamus tinctorius seed (CT-E/E) inhibited the production of NO and prostaglandin $E_2$ ($PGE_2$), tumor necorsis factor-a (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), interleukin-6 (IL-6) expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2). At a 50 ${\mu}g/ml$ level of CT-E/E, $PGE_2$, iNOS and COX-2 inhibition activity were shown 60%, 38%, and 42%, respectively. In addition, CT-E/E reduced the release of inflammatory cytokines including TNF-${\alpha}$, IL-$1{\beta}$ and IL-6. These results suggest that Carthamus tinctorious seed extracts may be a potential anti-inflammatory therapeutic agent due to the significant effects on inflammatory factors.
Antigen is substance causing disease derived from pathogen. Living organism has the immune system in terms of defense mechanism against antigen. Antigen is processed through several pathways such as phagocytosis, antibody action, complement activation, and cytotoxins by NK or cytotoxic T lymphocyte via MHC molecule. Lymph node (LN) is comprised of the complicated 3 dimensional network and several stromal cells. Fibroblastic reticular cells (FRC) are distributed in T zone for interaction with T cells. FRC produces the extra cellular matrix (ECM) into LN for ECM reorganization against pathogen infections and secretes homing chemokines. However, it has not so much been known about the involvement of the antigen process of FRC. The present report is for the function of FRC on antigen process. For this, FRC was positioned with several infected situations such as co-culture with macrophage, T cell, lipopolysaccharide (LPS) and TNFα stimulation. When co-culture between FRC with macrophage and T cells was performed, morphological change of FRC was observed and empty space between FRCs was made by morphological change. The matrix metallo-proteinase (MMP) activity was up-regulated by Y27632 and T cells onto FRC. Furthermore, inflammatory cytokine, TNFα regulated the expression of adhesion molecules and MHC I antigen transporter in FRC by gene chip assay. NO production was elevated by FRC monolayer co-cultured with macrophage stimulated by LPS. GFP antigen was up-taken by macrophage co-cultured with FRC. Collectively, it suggests that FRC assists of the facilitation of antigen process and LN stroma is implicated into antigen process pathway.
Journal of the Korean Applied Science and Technology
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v.33
no.4
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pp.717-725
/
2016
This study was designed to examine the in vitro antioxidant, antimicrobial and anti-inflammation effects of essential oils of Erigeron annuus L. Flower. Erigeron annuus L. essential oils were obtained by solvent extraction. Antioxidative ability was evaluated by bioassays using ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid diammonium salt) radical scavenging effect and 2, 2-diphenyl-1-1-picrydrazyl (DPPH) free radical scavenging activity. Erigeron annuus L. essential oil exhibited free radical scavenging activity on ABTS and DPPH 98.6%, 48.3% respectively, at a concentration of $500{\mu}g/ml$. Antimicrobial activity of essential oils of Erigeron annuus L. were tested against Staphylococcus aureus (S. aureus), Propionibacterium acnes (P. acne) and Escherichia coli (E. coli) by paper disc method, MIC and MBC. Erigeron annuus L. essential oil showed excellent antibacterial activities against S. aureus with MIC and MBC values of 0.31 mg/mL. The clear zone, indicating antimicrobial activity against P. acnes, was 14 mm, MIC and MBC values 0.31 mg/mL, 0.63 mg/mL, respectively. For the anti-inflammatory activity in RAW 264.7 cell, the Erigeron annuus L. essential oils inhibited not only NO production but also the expression of pro-inflammatory cytokines such as, TNF-${\alpha}$, IL-6 in a dose-dependent manner. These results suggested that Erigeron annuus L. essential oils has considerable potential as a cosmetic ingredient with antioxidative, antimicrobial and anti-inflammation effects.
Kang, Jae Ran;Hwang, Cho Rong;Sim, Hye Jin;Kang, Min Jung;Kang, Sang Tae;Shin, Jung Hye
Journal of the Korean Society of Food Science and Nutrition
/
v.44
no.7
/
pp.983-992
/
2015
This study investigated the quality characteristics and biological activities, such as antioxidant, whitening, anti-diabetes, and anti-inflammatory activities, of yellow garlic, by simplify processing time and manufacturing process compared with black garlic. Extracts were prepared various ratios of water and ethanol solvent [water : ethanol (v/v)=100:0, 70:30, 50:50, 30:70, 0:100] from yellow garlic. Alliin content of yellow garlic showed no difference compared with fresh garlic, whereas S-allyl cysteine content of yellow garlic was higher than that of fresh garlic. Alliin content of yellow garlic extracts increased in an ethanol concentration-dependent manner. Total phenol and flavonoid contents were highest in 100% ethanol extract. DPPH and ABTS radical scavenging abilities did not show significant differences among 0~70% ethanol extracts, whereas 100% ethanol extract showed the highest contents of 93.45% and 91.46%, respectively. Tyrosinase and ${\alpha}$-glucosidase inhibitory activities were also highest in 100% ethanol extract, but did not show significant differences among the extract solvents. Water and ethanol extracts from yellow garlic showed anti-inflammatory effects by modulating production of NO and cytokines at a concentration of $100{\mu}g/mL$. We suggest that yellow garlic has antioxidant, whitening, anti-diabetes, and anti-inflammatory activities and can be used as a functional material similar to black garlic.
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