• Journal of Yeungnam Medical Science
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• v.34 no.2
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• pp.149-160
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• 2017

Streptococcus pneumoniae, pneumococcus, is the most common cause of community-acquired pneumonia (CAP). CAP is an important infectious disease with high morbidity and mortality, and it is still one of the leading causes of death worldwide. Many genetic factors of the host and various environmental factors surrounding it have been studied as important determinants of the pathophysiology and outcomes of pneumococcal infections. Various cytokines, including transforming growth factor $(TGF)-{\beta}1$, are involved in different stages of the progression of pneumococcal infection. $TGF-{\beta}1$ is a cytokine that regulates a wide range of cellular and physiological functions, including immune and inflammatory responses. This cytokine has long been known as an anti-inflammatory cytokine that is critical to preventing the progression of an acute infection to a chronic condition. On the other hand, recent studies have unveiled the diverse roles of $TGF-{\beta}1$ on different stages of pneumococcal infections other than mitigating inflammation. This review summarizes the recent findings of the role of $TGF-{\beta}1$ on the pathophysiology of pneumococcal infections, which is fundamental to developing novel therapeutic strategies for such infections in immune-compromised patients.

• Toxicological Research
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• v.27 no.2
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• pp.71-76
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• 2011

We demonstrate that baicalein, a bioactive flavonoid originally isolated from Scutellaria baicalensis, inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Treatment of peritoneal macrophages and RAW 264.7 cells with baicalein inhibited LPS-stimulated nitric oxide production in a dose-related manner. Immunohistochemical staining of iNOS and RT-PCR analysis showed that the decrease of NO was due to the inhibition of iNOS gene expression in RAW 264.7 cells. Immunostaining of p65, EMSA, and reporter gene assay showed that baicalein inhibited NF-${\kappa}$B nuclear translocation, DNA binding, and transcriptional activation, respectively. Collectively, these series of experiments indicate that baicalein inhibits iNOS gene expression by blocking NF-${\kappa}$B nuclear translocation. Due to the critical role that NO release plays in mediating inflammatory responses, the inhibitory effects of baicalein on iNOS suggest that baicalein may represent a useful anti-inflammatory agent.

• Korean Journal of Acupuncture
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• v.36 no.4
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• pp.189-199
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• 2019

Objectives : This study aimed to investigate the effects of electroacupuncture (EA), the laser acupuncture (LA) and the combination therapy (LA+EA) in a collagenase-induced osteoarthritis rat model. Methods : Osteoarthritis rat model was induced by injection of collagenase into left lower articular cavity (50 μl to knee and 10 μl to ankle). In order to assess the anti-osteoarthritic effects of EA, the 650 nm LA and 650 nm LA+EA, the histopathological findings and plantar withdrawal responses were analyzed. Results : All of the treatment methods used in this study were effective in reducing pain. All treatment groups were effective in decreasing inflammatory cytokines of TNF-a and IL-6; the 650 nm LA and 650 nm LA+EA groups significantly reduced IL-1β. Conclusions : 650 nm LA and EA inhibit the production of collagenase-induced inflammatory mediators of osteoarthritis.

• Toxicological Research
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• v.32 no.2
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• pp.109-114
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• 2016

Allergic skin inflammation such as atopic dermatitis is characterized by skin barrier dysfunction, edema, and infiltration with various inflammatory cells. The anti-inflammatory effects of Apo-9'-fucoxanthinone, isolated from Sargassum muticum, have been described in many diseases, but the mechanism by which it modulates the immune system is poorly understood. In this study, the ability of Apo-9'-fucoxanthinone to suppress allergic reactions was investigated using a mouse model of atopic dermatitis. The Apo-9'-fucoxanthinone-treated group showed significantly decreased immunoglobulin E in serum. Also, Apo-9'-fucoxanthinone treatment resulted in a smaller lymph node size with reduced the thickness and length compared to the induction group. In addition, Apo-9'-fucoxanthinone inhibited the expression of interleukin-4, interferon-gamma and tumor necrosis factor-alpha by phorbol 12-myristate 13-acetate and ionomycin-stimulated lymphocytes. These results suggest that Apo-9'-fucoxanthinone may be a useful therapeutic strategy for treating chronic inflammatory diseases.

• Biomolecules & Therapeutics
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• v.16 no.3
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• pp.277-285
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• 2008

Panax ginseng C.A. Mayer (Araliaceae, P. ginseng) has been used for the enhancement of vascular and immune functions in Korea and Japan for a long time. Ginsenoside $Rb_1$ and $Rg_3$ isolated from P. ginseng head-part butanolic extract (PGHB) were investigated for anti-inflammatory activity. Ginsenosides and PGHB did not affect the cell viability within $0\;-\;100\;{\mu}g/ml$ concentration to RAW 264.7 murine macrophage cells. Ginsenosides and PGHB inhibited partly lipopolysaccharide (LPS)-induced nitrite production in a dose-dependent manner. The ginsenosides and PGHB showed partially chemical nitric oxide (NO) quenching (maximum 40%) in the cell-free system. Also, ginsenoside $Rb_1$ and $Rg_3$ inhibited markedly approximately 74 and 54% of inducible nitric oxide synthase (iNOS) mRNA transcription from LPS-induced RAW 264.7 cells. Taken together, the inhibitory effect of ginsenosides and PGHB on NO production did not occur as a result of cell viability, but was caused by both the chemical NO quenching and the regulation of iNOS. Additionally, the ginsenoside $Rb_1$ and PGHB inhibited prostaglandin $E_2$ ($PGE_2$) synthesis in a concentration-dependent manner, showed approximately 70-98% inhibition at $100\;{\mu}g/ml$ concentration. And the treatment with ginsenosides and PGHB attenuated partially LPS-upregulated cyclooxygenase-2 (COX-2) gene transcription. Ginsenoside $Rg_3$ suppressed LPS-stimulated interleukin-6 (IL-6) level to the basal in RAW 264.7 cells. From these results, ginsenoside $Rb_1,\;Rg_3$, and PGHB may be useful for the relief and retardation of immunological inflammatory responses and its action may occur through the reduction of inflammatory mediators, including NO, $PGE_2$, and IL-6 production.

• Parasites, Hosts and Diseases
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• v.55 no.6
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• pp.587-599
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• 2017

The immune response against Trichinella spiralis at the intestinal level depends on the $CD4^+$ T cells, which can both suppress or promote the inflammatory response through the synthesis of diverse cytokines. During the intestinal phase, the immune response is mixed (Th1/Th2) with the initial predominance of the Th1 response and the subsequent domination of Th2 response, which favor the development of intestinal pathology. In this context, the glucocorticoids (GC) are the pharmacotherapy for the intestinal inflammatory response in trichinellosis. However, its therapeutic use is limited, since studies have shown that treatment with GC suppresses the host immune system, favoring T. spiralis infection. In the search for novel pharmacological strategies that inhibit the Th1 immune response (proinflammatory) and assist the host against T. spiralis infection, recent studies showed that resiniferatoxin (RTX) had anti-inflammatory activity, which decreased the serum levels of IL-12, $INF-{\gamma}$, $IL-1{\beta}$, $TNF-{\alpha}$, NO, and $PGE_2$, as well the number of eosinophils in the blood, associated with decreased intestinal pathology and muscle parasite burden. These researches demonstrate that RTX is capable to inhibit the production of Th1 cytokines, contributing to the defense against T. spiralis infection, which places it as a new potential drug modulator of the immune response.

• Parasites, Hosts and Diseases
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• v.57 no.4
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• pp.379-387
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• 2019

Clonorchis sinensis is a carcinogenic human liver fluke that promotes hepatic inflammatory environments via direct contact or through their excretory-secretory products (ESPs), subsequently leading to cholangitis, periductal fibrosis, liver cirrhosis, and even cholangiocarcinoma (CCA). This study was conducted to examine the host inflammatory responses to C. sinensis ESPs and their putative protein components selected from C. sinensis expressed sequenced tag (EST) pool databases, including $TGF-{\beta}$ receptor interacting protein 1(CsTRIP1), legumain (CsLeg), and growth factor binding protein 2 (CsGrb2). Treatment of CCA cells (HuCCT1) with the ESPs or bacterial recombinant C. sinensis proteins differentially promoted the secretion of proinflammatory cytokines ($IL-1{\beta}$, IL-6, and $TNF-{\alpha}$) as well as anti-inflammatory cytokines (IL-10, $TGF-{\beta}1$, and $TGF-{\beta}2$) in a time-dependent manner. In particular, recombinant C. sinensis protein treatment resulted in increase (at maximum) of ~7-fold in $TGF-{\beta}1$, ~30-fold in $TGF-{\beta}2$, and ~3-fold in $TNF-{\alpha}$ compared with the increase produced by ESPs, indicating that CsTrip1, CsLeg, and CsGrb2 function as strong inducers for secretion of these cytokines in host cells. These results suggest that C. sinensis ESPs contribute to the immunopathological response in host cells, leading to clonorchiasis-associated hepatobiliary abnormalities of greater severity.

• BMB Reports
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• v.55 no.8
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• pp.389-394
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• 2022

In particular, the phenomenon of c-Jun degradation within the inflammatory response has not yet been fully analyzed. In order to verify this, we investigated LPS-stimulated murine macrophages pre-treated with sodium orthovanadate (SO) in order to uncover the regulatory mechanisms of the MAPKs which regulate c-Jun degradation within the inflammatory response. Through our study, we found that SO suppressed the production of prostaglandin E₂ (PGE₂) and the expression of COX-2 in LPS-stimulated RAW264.7 cells. Additionally, SO decreased total c-Jun levels, without altering the amount of mRNA, although the phospho-levels of p38, ERK, and JNK were strongly enhanced. Through the usage of selective MAPK inhibitors, and knockdown and overexpression strategies, p38 was revealed to be a major MAPK which regulates c-Jun degradation. Further analysis indicates that the phosphorylation of p38 is a determinant for c-Jun degradation, and is sufficient to induce ubiquitination-dependent c-Jun degradation, recovered through MG132 treatment. Therefore, our results suggest that the hyperphosphorylation of p38 by SO contributes to c-Jun degradation, which is linked to the suppression of PGE₂ secretion in inflammatory responses; and thus, finding drugs to increase p38 activity could be a novel strategy for the development of anti-inflammatory drugs.

• Korean Journal of Agricultural Science
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• v.45 no.3
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• pp.437-446
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• 2018

Lactoferrin is an iron-binding glycoprotein which is present in colostrum, milk, and other body secretions. Lactoferrin activities are associated with inflammatory and immune responses. The aim of this study was to investigate the effect of lactoferrin hydrolysates (LH) on the production of immunomodulatory factors such as inflammatory related cytokines (tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, interleukin (IL)-6, and interleukin (IL)-13) in Raw264.7 cells, which originated from murine macrophages. The results show that the Raw264.7 cells cultured in 3 types (whole, and above and below 10 kDa) of lactoferrin hydrolysates (LH) did not show any cytotoxicity in the cells. $TNF-{\alpha}$ decreased dose-dependently to 1,500 - 2,000 ng/mL by treatment with the 3 types of LH at 1, 50, $100{\mu}g/mL$, whereas the positive control, lipopolysaccharide (LPS), and negative control produced 2,450 and 1,000 ng/mL of $TNF-{\alpha}$, respectively, in the Raw264.7 cells. The treatment with the 3 types of LH (whole and above and below 10 kDa) at $50{\mu}g/mL$ produced about 20 - 28 ng/mL of $IL-1{\beta}$ at 3, 6, and 9 h, respectively, while the negative control produced 7 ng/mL, and LPS as the positive control produced 48 - 60 ng/mL. $TNF-{\alpha}$ and IL-6 expression was decreased dose-dependently by the 3 types of LH. The mRNA levels of IL-13 were slightly increased dose-dependently by the whole and above 10 kDa LH, but decreased dose-dependently by the below 10 kDa LH in the Raw264.7 cells. The results show that LH had immunomodulating effects on cytokine production in anti- and pro-inflammatory reactions as well as anti-allergic reactions.

• Nutrition Research and Practice
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• v.15 no.6
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• pp.798-806
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• 2021

BACKGROUND/OBJECTIVES: Obesity is associated with chronic inflammation. The spleen is the largest organ of the lymphatic system and has an important role in immunity. Obesity-induced inflammatory responses are triggered by Toll-like receptor (TLR)-myeloid differentiation primary response 88 (MyD88) pathway signaling. Phenethyl isothiocyanate (PEITC) and 3,3'-diindolylmethane (DIM), major dietary glucosinolates present in cruciferous vegetables, have been reported to produce anti-inflammatory effects on various diseases. However, the effects of PEITC and DIM on the obesity-induced inflammatory response in the spleen are unclear. The purpose of this study was to examine the anti-inflammatory effects of PEITC and DIM on the spleen and their mechanism in high fat/cholesterol diet (HFCD)-fed C57BL/6 mice. MATERIALS/METHODS: We established an animal model of HFCD-induced obesity using C57BL/6 mice. The mice were divided into six groups: normal diet with AIN-93G diet (CON), high fat diet (60% calories from fat) with 1% cholesterol (HFCD), HFCD with PEITC 30 mg/kg/day or 75 mg/kg/day (HFCD+P30, HFCD+P75), and HFCD with DIM 1.5 mg/kg/day or 7.5 mg/kg/day (HFCD+D1.5, HFCD+D7.5). Enzyme-linked immunosorbent assay was used to evaluate pro-inflammatory cytokine secretion. Western blot and quantitative polymerase chain reaction were used to analyze protein and mRNA levels of nuclear factor kappa B (NF-κB) p65, interleukin 6 (IL-6), cyclooxygenase 2 (COX-2), TLR2, TLR4, and MyD88 in spleen tissue. RESULTS: Serum IL-6 levels were significantly higher in the HFCD group than in groups fed a HFCD with PEITC or DIM. Levels of NF-κB p65 protein and TLR2/4, MyD88, NF-κB p65, IL-6, and COX-2 mRNA were significantly higher in the HFCD group than in the CON group and were reduced by the PEITC and DIM supplements. CONCLUSIONS: PEITC- and DIM-supplemented diets improved splenic inflammation by modulating the TLR2/4-MyD88 pathway in HFCD-fed mice. We suggest that dietary glucosinolates may at least partially improve obesity-induced inflammation of the spleen.