• Molecules and Cells
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• v.26 no.1
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• pp.67-73
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• 2008

Herpetic stromal keratitis (HSK) is an inflammatory disorder induced by HSV-1 infection and characterized by T cell-dependent destruction of corneal tissues. It is not known what triggers $CD4^+$ T cell migration into the stroma of HSV-1-infected corneas. The keratocyte is a fibroblast-like cell that can function as an antigen-presenting cell in the mouse cornea by expressing MHC class II and costimulatory molecules after HSV-1 infection. We hypothesized that chemokines produced by stromal keratocytes are involved in $CD4^+$ T cell infiltration into the cornea. We found that keratocytes produce several cytokines and chemokines, including MCP-1, RANTES, and T cell activation (TCA)-3. HSV-1 infection increased the production of MCP-1 and RANTES by keratocytes, and these acted as chemoattractants for HSV-1-primed $CD4^+$ T cells expressing CCR2 and CCR5. ExpreHerpetic stromal keratitis (HSK) is an inflammatory disorder induced by HSV-1 infection and characterized by T cell-dependent destruction of corneal tissues. It is not known what triggers $CD4^+$ T cell migration into the stroma of HSV-1-infected corneas. The keratocyte is a fibroblast-like cell that can function as an antigen-presenting cell in the mouse cornea by expressing MHC class II and costimulatory molecules after HSV-1 infection. We hypothesized that chemokines produced by stromal keratocytes are involved in $CD4^+$ T cell infiltration into the cornea. We found that keratocytes produce several cytokines and chemokines, including MCP-1, RANTES, and T cell activation (TCA)-3. HSV-1 infection increased the production of MCP-1 and RANTES by keratocytes, and these acted as chemoattractants for HSV-1-primed $CD4^+$ T cells expressing CCR2 and CCR5. Expression of MCP-1 in the corneal stroma was confirmed in vivo. Finally, when HSV-1-primed $CD4^+$ T cells were adoptively transferred into wild type and MCP-1-deficient mice that had been sublethally irradiated to minimize chemokine production from immune cells, infiltration of $CD4^+$ T cells was markedly reduced in the MCP-1-deficient mice, suggesting that it is the MCP-1 from HSV-1-infected keratocytes that attracts $CD4^+$ T cells into the cornea.

• Korean Journal of Acupuncture
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• v.24 no.3
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• pp.179-204
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• 2007

Objectives & Methods : The purpose of this study is to observe the effects of Angelicae Radix Pharmacopuncture(AR-P) at Joksamni(ST36) on collagen II induced arthritis in DBA/1J mice. The authors evaluated arthritis index, arthritis incidence and joint edema, and measured body weight, spleen size and stenosis rate, serum cytokine level, serum antibody level, immune cell populations In spleen, lymph node, and knee joint, and performed histological analysis of CIA mouse joint. Results : In the AR-P group, arthritis index, arthritis incidence and joint edema were decreased, and the enlargement, malformation and stenosis of spleen and the malformation of joint appeared milder than the control group. In AR-P group, the levels of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, $IFN-{\gamma}$ in serum were significantly decreased. And the level of anti-collagen II in serum was maintained lower in AR-P group than in the control group. In AR-P group, the level of $IFN-{\gamma}$ and IL-10, and $IFN-{\gamma}/IL-4$ ratio were significantly decreased, and the ratios of $CD3e^+$ cells to $CD45^+$ cells, $CD4^+$ cells to $CD8^+$ cells in spleen were similarly maintained as those of the normal group. In the AR-P group, the populations of $CD4^+/CD25^+$ cells in spleen and lymph nodes, $CD45R^+/CD69^+$ cells in lymph nodes, $CD3^+/CD69^+$ cells and $CD11b^+/Gr-1^+$ cells in knee joint were decreased. In the histological analysis, the cartilage destruction, synovial cell proliferation and the collagen fiber destruction were decreased in the AR-P group Conclusions : The results suggest that AR-P at right ST36 has a therapeutic effect on collagen-induced arthritis in mice.

• Korean Journal of Korean Medical Institute of Dermatology and Aesthetics
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• v.1 no.1
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• pp.53-90
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• 2005

Purpose: Contents of astragaloside I, II and IV, cytotoxicity, anticancer activity, immunomodulatory activity and antioxidant capacity were to be compared as a function of the cultivated years as one, three, five and seven years. Method: Major components of Astragali membranacei Radix were separated as astragaloside I, astragaloside II, astragaloside IV by HPLC analysis. Cytotoxicity and anticancer activities were measured by MTT and SRB assay. For immunomodulatory activity, the secretion of IL -6 and $TNF-{\alpha}$, NK cell activation and macrophage activation were observed as well as kinetics of responding to human T cells by a microphysiometer. In vitro antioxidant activities were measured by several radical scavenging activities of superoxide anion radican, DPPH, LDL and linoleic acid. For in vivo activity, the activation of SOD, GSH-px, catalase, ALDH and ADH was measured as well the relative weight of liver. Result : 1. For HPLC analysis, the contents of all of astragaloside I, astragaloside II, astragaloside IV were in order of three, five, one and seven years. 2. The cytotoxicity of normal human lung cell line, HEL299 showed lower than 18% in adding 0.25 mg/ml, and 28.9% in adding 1.0 mg/ml of water extract of seven year root. For methanol extracts, three year root showed highest cytotoxicity as 35.2 % and there was no difference between the cultivated years. 3. For anticancer activities, methanol extracts of one and three year roots showed relatively high inhibition of human stomach cancer cells, AGS, breast cancer cells, MCF-7, lung cancer cells, A549 and liver cancer cell, Hep3B as well as high selectivities. 4. The water extract of seven year root could yield high secretion of IL-6 from both human Band T cells while the methanol extracts of three and five year roots secreted high amounts of IL-6 and $TNF-{\alpha}$ from both Band T cells. 5. As a result of in vitro antioxidant activities, both water and methanol extracts from five and seven year roots showed high activities for superoxide anion radical scavenging activity, inhibiting linoleic acid peroxide and contents of total phenols. 6. For in vivo tests, Mn-SOD and GSH-px activities and weight of liver were better in adding seven year root. For ALDH activity one year root was better and for ADH activity five year root. Overall speaking, seven year root showed relatively better antioxidant activities. Conclusion:There was difference of the contents of astragaloside I, astragaloside II, astragaloside IV according to cultivation year. Methanol extract showed better activities of anticancer and immune activation rather than water extract Interestingly enough, for methanol extracts, overall activities were improved as the cultivation year increased. There might be further investigation required for the clinical uses of the results as several biological activities varied according to the cultivated year of Astragali membranacei Radix.

• Restorative Dentistry and Endodontics
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• v.34 no.6
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• pp.537-550
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• 2009

During the last two decades, there has been an increasing interest in the impact of oral health on atherosclerosis and subsequent cardiovascular disease (CVD). To date, some periodontal pathogens including Porphyromonas gingivalis (P. gingivalis) have been reported to be relevant to CVD. Porphyromonas endodontalis (P. endodontalis), which shares approximately 87% sequence homology with P. gingivalis, is mostly found within infected root canals. However, recent studies reveal that this pathogen also resides in the dental plaque or periodontal pocket in patients with periodontitis. It has been shown that P. endodontalis invades human coronary artery endothelial cells (HCAEC) and coronary artery smooth muscle cells (CASMC). To evaluate whether P. endodontalis can participate in the progression of atherosclerosis and CVD, we examined the changes in transcriptional gene expression profiles of HCAEC responding to invaion by P. endodontalis in this study. The following results were obtained. 1. Porphyromonas endodontalis was invasive of HCAEC. 2. According to the microarray analysis, there were 625 genes upregulated more than two-folds, while there were 154 genes downregulated by half. 3. Upregulated genes were relevant to inflammatory cytokines, apoptosis, coagulation and immune response. Enhanced expression of MMP-1 was also noticeable. 4. The transcription profiles of the 10 selected genes examined by real-time PCR agreed well with those observed in the microarray analysis. Thus, these results show that P. endodontalis presents the potential to trigger and augment atherosclerosis leading to CVD.

• Korean Journal of Medicinal Crop Science
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• v.25 no.5
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• pp.269-281
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• 2017

Background: Small particles increase airway inflammation upon reaching the alveoli. Here, we investigated the protective or therapeutic effects of Salvia plebeia R. Br. (SP_R) extracts on airway inflammation. Methods and Results: To investigate the anti-inflammatory activity of SP_R extracts, we measured their inhibitory effect on the production of reactive oxygen species (ROS) expression of inflammatory mediators, and immune cell infiltration in MH-S alveolar macrophage cells and in the ambient particulate matter (APM)-exposed airway inflammation mice model. The SP_R extracts inhibited the production of ROS and expression of IL-4, IL-10, IL-15, and IL-17A mRNA in APM-stimulated MH-S cells. Oral administration of SP_R extracts suppressed APM-induced inflammatory symptoms, such as high alveolar wall thickness, excess collagen fibers, decreased mRNA expression of chemokines (Ccr9, Ccl5, Ccr3), inflammatory cytokines (IL-15, TNF-${\alpha}$), and IL-4 Th2 cytokine in the lung. The SP_R extracts also inhibited ROS production, granulocyte ($CD11b^+Gr-1^+$) infiltration, IL-17A, TNF-${\alpha}$, macrophage inflammatory protein (Mip-2), and chemokine (C-X-C motif) ligand 1 (Cxcl-1) production in the airway. The specific compounds in the SR-R extracts that mediate the anti-inflammatory effects were identified. Conclusions: In this study, SP_R extracts effectively inhibited airway inflammatory responses, such as ROS production and granulocyte infiltration into the airway, by regulating the expression of chemokines and inflammatory cytokines.

• Biomolecules & Therapeutics
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• v.25 no.3
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• pp.266-271
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• 2017

Synthetic cannabinoids are one of most abused new psychoactive substances. The recreational use of abused drug has aroused serious concerns about the consequences of these drugs on infection. However, the effects of synthetic cannabinoid on resistance to tetanus toxin are not fully understood yet. In the present study, we aimed to determine if the administration of synthetic cannabinoids increase the susceptibility to tetanus toxin-induced motor behavioral deficit and functional changes in cerebellar neurons in mice. Furthermore, we measured T lymphocytes marker levels, such as CD8 and CD4 which against tetanus toxin. JWH-210 administration decreased expression levels of T cell activators including cluster of differentiation (CD) $3{\varepsilon}$, $CD3{\gamma}$, CD74p31, and CD74p41. In addition, we demonstrated that JWH-210 induced motor impairment and decrement of vesicle-associated membrane proteins 2 levels in the cerebellum of mice treated with tetanus toxin. Furthermore, cerebellar glutamatergic neuronal homeostasis was hampered by JWH-210 administration, as evidenced by increased glutamate concentration levels in the cerebellum. These results suggest that JWH-210 may increase the vulnerability to tetanus toxin via the regulation of immune function.

• Korean Journal of Food Science and Technology
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• v.53 no.5
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• pp.570-577
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• 2021

This study elucidated the biological activities and structural characteristics of polysaccharides isolated from ginseng leaves fermented using Cordyceps sinensis (GLF). GLF comprised at least 18 glycosyl linkages, including 4-linked glucose residues (24.0%). To characterize the neutral polysaccharides in GLF, it was further fractionated by anion exchange chromatography, and the unabsorbed fraction (GLF1) was isolated. Peritoneal macrophages stimulated with GLF1 produced various cytokines in a dose-dependent manner. The properties and activities of the four subfractions (PHI, PHIA1-PHIA3) obtained after sequential enzymatic digestion were examined. PHI and PHIA3 primarily comprised glucose, whereas PHI exhibited an iodine-color reaction. Furthermore, the PHIA1-3 fractions indicated that cytokine production was completely inhibited. These results suggest at the immune activities of GLF1 may be due to the α-(1→4)-glucan branched at the C(O)6 position, which was produced by C. sinensis.

• Journal of Veterinary Science
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• v.22 no.3
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• pp.39.18-39.18
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• 2021

Background: Interferon lambda receptor 1 (IFNLR1) is a type II cytokine receptor that clings to interleukins IL-28A, IL29B, and IL-29 referred to as type III IFNs (IFN-λs). IFN-λs act through the JAK-STAT signaling pathway to exert antiviral effects related to preventing and curing an infection. Although the immune function of IFN-λs in virus invasion has been described, the molecular mechanism of IFNLR1 in that process is unclear. Objectives: The purpose of this study was to elucidate the role of IFNLR1 in the pathogenesis and treatment of porcine reproductive and respiratory syndrome virus (PRRSV). Methods: The effects of IFNLR1 on the proliferation of porcine alveolar macrophages (PAMs) during PRRSV infection were investigated using interference and overexpression methods. Results: In this study, the expressions of the IFNLR1 gene in the liver, large intestine, small intestine, kidney, and lung tissues of Dapulian pigs were significantly higher than those in Landrace pigs. It was determined that porcine IFNLR1 overexpression suppresses PRRSV replication. The qRT-PCR results revealed that overexpression of IFNLR1 upregulated antiviral and IFN-stimulated genes. IFNLR1 overexpression inhibits the proliferation of PAMs and upregulation of p-STAT1. By contrast, knockdown of IFNLR1 expression promotes PAMs proliferation. The G0/G1 phase proportion in IFNLR1-overexpressing cells increased, and the opposite change was observed in IFNLR1-underexpressing cells. After inhibition of the JAK/STAT signaling pathway, the G2/M phase proportion in the IFNLR1-overexpressing cells showed a significant increasing trend. In conclusion, overexpression of IFNLR1 induces activation of the JAK/STAT pathway, thereby inhibiting the proliferation of PAMs infected with PRRSV. Conclusion: Expression of the IFNLR1 gene has an important regulatory role in PRRSV-infected PAMs, indicating it has potential as a molecular target in developing a new strategy for the treatment of PRRSV.

• Journal of Animal Science and Technology
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• v.63 no.6
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• pp.1362-1375
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• 2021

This study was conducted to evaluate the efficacy of a combination 3,4,5-trihydroxybenzoic acid (THB) and oregano extracts (i.e., Carvacrol and Thymol) at intake/dietary different levels on growth performance, intestinal health indicators, immune responses and fecal oocyst shedding in broiler chickens under Eimeria challenged condition. A total of 336 one-day-old broilers were randomly assigned to one of six dietary treatments with seven replications per treatment. Dietary treatments were: i) Non-challenged bird without any dietary treatment (NCNT), ii) Challenged bird without any dietary treatment (CNT), iii) Challenged birds fed a THB diet (0.1 g/kg, THB), iv) Challenged birds fed a combination of THB and oregano extracts diet (0.1 g/kg, COM 100), and a gradual increase of combination of THB and oregano extracts likely v) 0.15 g/kg (COM 150), and 0.2 g/kg (COM 200). On day 14, all groups except for NCNT have orally challenged with a 10-fold dose of Livacox^® T anticoccidial vaccine to trigger coccidiosis. The results indicated that Eimeria-challenged broilers fed COM 100 and COM 200 diets increased (p < 0.05) body weight than CNT diet on day 35. Furthermore, birds fed COM 100 and COM 200 diets increased (p < 0.05) average daily gain compared to those fed CNT diets for the entire experimental period. There is no significant (p > 0.05) in average daily feed intake, feed efficiency between NCNT and birds fed with combined THB and oregano extracts for the entire experimental period. A combination of THB and oregano extract regardless of concentration levels or THB alone reduced (p < 0.05) lesion score in ileum compared to the CNT diet for 7 days post-infection (dpi). Birds fed COM 100 diet had lower (p < 0.05) intestinal lesion scores in jejunum and caeca on 7 dpi compared to those were in the CNT diet. No (p > 0.05) difference was observed in the oocysts per gram of feces count, intestinal morphology, carcass traits and blood cytokine concentration among the infected treatments. Collectively, we conclude that birds fed with a combination of THB and oregano extracts regardless of the ratios that were used demonstrated better recovery of health after the coccidial challenge than using only THB alone.

• Journal of Microbiology and Biotechnology
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• v.29 no.2
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• pp.330-338
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• 2019

Chronic infection with intracellular Brucella abortus (B. abortus) in livestock remains as a major problem worldwide. Thus, the search for an ideal vaccine is still ongoing. In this study, we evaluated the protective efficacy of a combination of B. abortus recombinant proteins; superoxide dismutase (rSodC), riboflavin synthase subunit beta (rRibH), nucleoside diphosphate kinase (rNdk), 50S ribosomal protein (rL7/L12) and malate dehydrogenase (rMDH), cloned and expressed into a pMal vector system and $DH5{\alpha}$, respectively, and further purified and applied intraperitoneally into BALB/c mice. After first immunization and two boosters, mice were infected intraperitoneally (IP) with $5{\times}10^4CFU$ of virulent B. abortus 544. Spleens were harvested and bacterial loads were evaluated at two weeks post-infection. Results revealed that this combination showed significant reduction in bacterial colonization in the spleen with a log protection unit of 1.31, which is comparable to the average protection conferred by the widely used live attenuated vaccine RB51. Cytokine analysis exhibited enhancement of cell-mediated immune response as IFN-${\gamma}$ is significantly elevated while IL-10, which is considered beneficial to the pathogen's survival, was reduced compared to control group. Furthermore, both titers of IgG1 and IgG2a were significantly elevated at three and four-week time points from first immunization. In summary, our in vivo data revealed that vaccination with a combination of five different proteins conferred a heightened host response to Brucella infection through cell-mediated immunity which is desirable in the control of intracellular pathogens. Thus, this combination might be considered for further improvement as a potential candidate vaccine against Brucella infection.