• The Korea Journal of Herbology
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• v.28 no.1
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• pp.43-50
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• 2013

Objectives : Hwanggeumjakyak-tang (huangqin shaoyao tang, HJT) has been used to treat acute enteritis in traditional oriental medicine. However, there has been a lack of studies regarding the effects of HJT on the inflammatory activities and effector inflammatory disease mechanism about macrophage before is not known. So we examined the effect of HJT water extract on pro-inflammatory mediators in lipopolysaccharide (LPS) - stimulated mouse macrophage, RAW 264.7 cells. Methods : Cells were treated with 2 ug/mL of LPS 1 h prior to the addition of HJT. Cell viability was measured by MTS assay. The production of nitric oxide (NO) was determined by reacting cultured medium with Griess reagent. The expression of cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS) and mitogen-activated protein kinases (MAPKs) was investigated by Western blot, RT-PCR. The content of level of cytokines (prostaglandin (PG) $E_2$, interleukin (IL)-6, IL-12, Tumor necrosis factor-alpha (TNF-${\alpha}$) and monocyte chemoattractant protein-1 (MCP-1)) in media from LPS-stimulated Raw 264.7 cells was analyed by ELISA kit. Results : HJT inhibited the production of NO, $PGE_2$, IL-6 as well as the expressions of iNOS, COX-2 but did not inhibit the production of IL-12, TNF-${\alpha}$, MCP-1 in the murine macrophage, RAW 264.7 cells. HJT also had suppression effects of LPS-induced MAPKs activation Conclusion : These results suggest that HJT has an anti-inflammatory therapeutic potential, which may result from inhibition of MAPK phosphorylation, thereby decreasing the expression of pro-inflammatory genes.

• Nutrition Research and Practice
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• v.2 no.2
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• pp.134-137
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• 2008

Atherosclerosis is characterized by a chronic inflammatory disease, and chemokines play an important role in both initiation and progression of atherosclerosis development. Leukotactin-1 (Lkn-1/CCLl5), a new member of the human CC chemokine family, is a potent chemoattractant for leukocytes. Our previous study has demonstrated that Lkn-1/CCL15 plays a role in the initiation of atherosclerosis, however, little is currently known whether Lkn-1/CCL15 is associated with the progression of atherosclerosis. Matrix metalloproteinases (MMPs) in human coronary atherosclerotic lesions playa crucial role in the progression of atherosclerosis by altering the vulnerability of plaque rupture. In the present study, we examined whether Lkn-1/CCLl5 modulates MMP-9 release, which is a prevalent form expressed by activated macrophages and foam cells. Human THP-1 monocytic cells and/or human peripheral blood monocytes (PBMC) were treated with phorbol myristate acetate to induce their differentiation into macrophages. Foam cells were prepared by the treatment of THP-1 macrophages with human oxidized LDL. The macrophages and foam cells were treated with Lkn-1/CCL15, and the levels of MMP-9 release were measured by Gelatin Zymography. Lkn-1/CCL15 significantly enhanced the levels of MMP-9 protein secretion from THP-1 monocytic cells-derived macrophages, human PBMC-derived macrophages, as well as macrophage-derived foam cell in a dose dependent manner. Our data suggest that the action of Lkn-1/CCL15 on macrophages and foam cells to release MMP-9 may contribute to plaque destabilization in the progression of atherosclerosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.5
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• pp.486-493
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• 2014

Adipocytes are endocrine cells that release bioactive mediators called adipokines. In condition of obesity characterized by low-grade chronic inflammation, adipocytes release inflammatory adipokines, which is related to insulin resistance. Bojungchiseub-tang (BJCST) has been used in symptoms and signs of edema, dampness-phlegm, kidney failure, and so on in Korean medicine. BJCST is also expected to have anti-obesity activities. In the present study, we examined whether BJCST modulate the production of inflammatory adipokines and the activations of the mitogen-activated protein kinases (MAPK) signaling pathway related to induce adipocyte inflammation to elucidate the effects and its mechanism of BJCST on lowering the content of inflammatory adipokines in 3T3-L1 adipocytes. As a result, BJCST suppressed the production of proinflammatory cytokines, tumor necrosis factor (TNF) $-{\alpha}$, interleukin (IL) $-1{\beta}$, IL-6, interferon (IFN) -${\gamma}$, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), and the production of other inflammatory mediators, prostaglandin $E_2(PGE_2)$ and nitric oxide(NO)viadownregulationofcyclooxygenase-2(COX-2)andinducible NO synthase (iNOS) gene expressions. In addition, BJCST decreased the phosphorylation of MAPK that promotes the production of inflammatory adipokines in 3T3-L1 mature adipocytes. In conclusion, BJCST could regulate the production of inflammatory adipokines and MAPK signaling pathway related to induction of adipose inflammation.

• Journal of Applied Biological Chemistry
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• v.63 no.2
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• pp.117-123
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• 2020

We examined the anti-inflammatory effect of the peel extract of the newly bred Korean apple (Malus domestica Borkh.) cultivar Green ball. To test its possible use as anti-inflammatory functional material, Raw 264.7 macrophages were treated with pro-inflammatory lipopolysaccharide (LPS) in the presence or absence of Green ball apple peel ethanol extract (GBE). Notably, up to 500 ㎍/mL of GBE did not result in any signs of inhibition on cellular metabolic activity or cytotoxicity in Raw 264.7 macrophages. Supplementation with GBE to LPS-treated Raw 264.7 macrophage significantly suppressed various pro-inflammatory responses in a dose-dependent manner, including i) nitric oxide (NO) production, ii) accumulation of inducible NO synthase and cyclooxygenase-2, iii) phosphorylation of nuclear factor-kappa B (NF-κB) subunit p65, and iv) expression of pro-inflammatory biomarker genes, including tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, monocyte chemoattractant protein-1, and prostaglandin E synthase 2.

• Nutrition Research and Practice
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• v.9 no.3
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• pp.235-241
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• 2015

BACKGROUND/OBJECTIVES: Doenjang, Korean traditional fermented soybean paste has been reported to have an anti-obesity effect. Because adipose tissue is considered a major source of inflammatory signals, we investigated the protective effects of Doenjang and steamed soybean on oxidative stress and inflammation in adipose tissue of diet-induced obese mice. MATERIALS/METHODS: Male C57BL/6J mice were fed a low fat diet (LF), a high-fat diet (HF), or a high-fat containing Doenjang diet (DJ) or a high-fat containing steamed soybean diet (SS) for 11 weeks. RESULTS: Mice fed a DJ diet showed significantly lower body and adipose tissue weights than those in the HF group. Although no significant differences in adipocyte size and number were observed among the HF diet-fed groups, consumption of Doenjang alleviated the incidence of crown-like structures in adipose tissue. Consistently, we observed significantly reduced mRNA levels of oxidative stress markers (heme oxygenase-1 and $p40^{phox}$), pro-inflammatory adipokines (tumor necrosis factor alpha and macrophage chemoattractant protein-1), macrophage markers (CD68 and CD11c), and a fibrosis marker (transforming growth factor beta 1) by Doenjang consumption. Gene expression of anti-inflammatory adipokine, adiponectin was significantly induced in the DJ group and the SS group compared to the HF group. The anti-oxidative stress and anti-inflammatory effects observed in mice fed an SS diet were not as effective as those in mice fed a DJ diet, suggesting that the bioactive compounds produced during fermentation and aging may be involved in the observed health-beneficial effects of Doenjang. CONCLUSIONS: Doenjang alleviated oxidative stress and restored the dysregulated expression of adipokine genes caused by excess adiposity. Therefore, Doenjang may ameliorate systemic inflammation and oxidative stress in obesity via inhibition of inflammatory signals of adipose tissue.

• Journal of Preventive Veterinary Medicine
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• v.42 no.4
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• pp.157-162
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• 2018

This study evaluated the protective effects of a combination of eight B. abortus recombinant proteins that were cloned and expressed into a pMal vector system and $DH5{\alpha}$: nucleoside diphosphate kinase (rNdk), 50S ribosomal protein (rL7/L12), malate dehydrogenase (rMDH), DNA starvation/stationary phase protection protein (rDps), elongation factor (rTsf), arginase (rRocF), superoxide dismutase (rSodC), and riboflavin synthase subunit beta (rRibH). The proteins were induced, purified, and administered intraperitoneally into BALB/c mice. The mice were immunized three times at weeks 0, 2, and 5 and then infected intraperitoneally (IP) with $5{\times}10^4CFU$ of virulent B. abortus 544 one week after the last immunization. The spleens were collected and the bacterial burden was evaluated at four weeks post-infection. The results showed that this combination produced a significant reduction of the bacterial burden in the spleen with a log reduction of 1.01 compared to the PBS group. Cytokine analysis revealed induction of the cell-mediated immune response in that TNF (tumor necrosis factor) and proinflammatory cytokines IL-6 (Interleukin 6) and MCP-1 (macrophage chemoattractant protein-1) were elevated significantly. In summary, vaccination with a combination of eight different proteins induced a significant protective effect indicative of a cell mediated immune response.

• The Journal of Korean Physical Therapy
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• v.21 no.3
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• pp.95-102
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• 2009

Purpose: This study evaluates MCP-1 expression in the dorsal horn of a rat model of lumbar disc herniation by an autograft of the nucleus pulposus to the spinal nerve. Methods: After a coccygeal nucleus pulposus graft to the left $5^{th}$ lumbar spinal nerve, proximal to dorsal root ganglion, mechanical allodynia and thermal hyperalgesia were assessed 1 day before surgery, and 1, 10, 20, 30 days after surgery. The mRNA of MCP-1 in the dorsal horn was assessed by real time PCR to compare the temporal pattern of neuropathic pain of the lumbar disc herniation model. Results: In the ipsilateral side of the lumbar disc herniation models, mechanical allodynia and thermal hyperalgesia reached a maximum at 10 days after surgery with significant difference from the control group. Pain was also provoked in the contralateral side of the lumbar disc herniation models with less intensity than the ipsilateral side. The level of MCP-1 mRNA expression in the dorsal horn reached a peak at 20 days after surgery. Conclusion: Mechanical allodynia and thermal hyperalgesia was induced by nucleus pulposus in a rat lumbar disc herniation model, similar to a previously reported peripheral nerve injury model. The level of MCP-1 expression was higher in the dorsal horn of the ipsilateral and contralateral sides. These results suggest that MCP-1 might play a role in the maintenance of neuropathic pain.

• Tuberculosis and Respiratory Diseases
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• v.81 no.4
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• pp.305-310
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• 2018

Background: Mannose-binding lectin (MBL) deficiency leads to increased susceptibility to infection. We investigated whether serial changes in MBL levels are associated with the prognosis of patients diagnosed with septic shock, and correlated with cytokine levels. Methods: We enrolled 131 patients with septic shock in the study. We analyzed the serum samples for MBL and cytokine levels at baseline and 7 days later. Samples on day 7 were available in 73 patients. Results: We divided the patients with septic shock into four groups according to serum MBL levels (< $1.3{\mu}g/mL$ or ${\geq}1.3{\mu}g/mL$) on days 1 and 7. Patients with low MBL levels on day 1 and high MBL levels on day 7 showed a favorable prognosis for 28-day survival (odds ratio, 1.96, 95% confidence interval, 1.10-2.87; p=0.087). The high MBL group on day 7 showed a significant decrease in monocyte chemoattractant protein 1, interleukin (IL)-$1{\beta}$, IL-6, IL-8, interferon-${\gamma}$, and granulocyte macrophage colony-stimulating factor levels compared with the low MBL group on day 7. Conclusion: The increase in MBL levels of patients with septic shock may suggest a favorable prognosis and attenuate pro-inflammatory and anti-inflammatory responses.

• Nutrition Research and Practice
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• v.16 no.5
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• pp.589-603
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• 2022

BACKGROUND/OBJECTIVES: Previous studies have reported that protein supplementation contributes to the attenuation of inflammation. Serious trauma such as burn injury usually results in the excessive release of inflammatory factors and organs dysfunction. However, a few reports continued to focus on the function of protein ingestion in regulating burn-induced inflammation and organ dysfunction. MATERIALS/METHODS: This study established the rat model of 30% total body surface area burn injury, and evaluated the function of blended protein (mixture of whey and soybean proteins). Blood routine examination, inflammatory factors, blood biochemistry, and immunohistochemical assays were employed to analyze the samples from different treatment groups. RESULTS: Our results indicated a decrease in the numbers of white blood cells, monocytes, and neutrophils in the burn injury group administered with the blended protein nutritional support (Burn+BP), as compared to the burn injury group administered normal saline supplementation (Burn+S). Expressions of the pro-inflammatory factors (tumor necrosis factor-α and interleukin-6 [IL-6]) and chemokines (macrophage chemoattractant protein-1, regulated upon activation normal T cell expressed and secreted factor, and C-C motif chemokine 11) were dramatically decreased, whereas anti-inflammatory factors (IL-4, IL-10, and IL-13) were significantly increased in the Burn+BP group. Kidney function related markers blood urea nitrogen and serum creatinine, and the liver function related markers alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase were remarkably reduced, whereas albumin levels were elevated in the Burn+BP group as compared to levels obtained in the Burn+S group. Furthermore, inflammatory cells infiltration of the kidney and liver was also attenuated after burn injury administered with blended protein supplementation. CONCLUSIONS: In summary, nutritional support with blended proteins dramatically attenuates the burn-induced inflammatory reaction and protects organ functions. We believe this is a new insight into a potential therapeutic strategy for nutritional support of burn patients.

• IMMUNE NETWORK
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• v.2 no.4
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• pp.223-226
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• 2002

Background: The type 2 deviated immunological state is predominant in lepromatous leprosy. Erythema nodosum leprosum (ENL) is an immune-complex mediated reaction that typically occurs in lepromatous leprosy. To date, the serum levels of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-2 receptor, IL-10, IL-$1{\beta}$, IL-1 receptor antagonist and monocyte chemoattractant protein-1 (MCP-1) were reported to be higher in lepromatous leprosy. TNF-${\alpha}$ is also known to be higher in ENL, which is reduced after thalidomide treatment. However the serum type 2 chemokine levels in lepromatous leprosy patients have not been reported. Methods: The serum levels of the type 2 chemokines such as thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and eotaxin together with IL-12 and IL-10 in the sera from leprosy patients were detected using an enzyme-linked solvent assay (ELISA) method. Results: The Serum TARC, MDC, eotaxin, IL-10 and IL-12 levels in lepromatous leprosy patients were not significantly different from the normal control levels. The serum levels were not significantly different between the paucibacillary group and multibacillary group. The serum TARC or MDC levels in the ENL patients were more reduced after a treatment containing thalidomide. Conclusion: The type 2 chemokines are not related to the severity of lepromatous leprosy. The larger reducing effect of the TARC or MDC levels in ENL patients by a treatment containing thalidomide suggests the potential role of these chemokines in the development of ENL and the therapeutic mechanism of thalidomide.