• BMB Reports
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• v.48 no.3
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• pp.172-177
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• 2015

Upregulation of pro-inflammatory mediators contributes to ${\beta}$-cell destruction and enhanced infiltration of immune cells into pancreatic islets during development of type 1 diabetes mellitus. In this study, we examined the regulatory effects and the mechanisms of action of celastrol against cytotoxicity and pro-inflammatory immune responses in the RINm5F rat pancreatic ${\beta}$-cell line stimulated with a combination of interleukin-1 beta, tumor necrosis factor-alpha, and interferon-${\gamma}$. Celastrol significantly restored cytokine-induced cell death and significantly inhibited cytokine-induced nitric oxide production. In addition, the protective effect of celastrol was correlated with a reduction in pro-inflammatory mediators, such as inducible nitric oxide synthase, cyclooxygenase-2, and CC chemokine ligand 2. Furthermore, celastrol significantly suppressed cytokine-induced signaling cascades leading to nuclear factor kappa B (NF-${\kappa}B$) activation, including $I{\kappa}B$-kinase (IKK) activation, $I{\kappa}B$ degradation, p65 phosphorylation, and p65 DNA binding activity. These results suggest that celastrol may exert its cytoprotective activity by suppressing cytokine-induced expression of pro-inflammatory mediators by inhibiting activation of NF-${\kappa}B$ in RINm5F cells.

• Journal of the Korean Applied Science and Technology
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• v.37 no.4
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• pp.762-768
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• 2020

This study aimed to investigate the effect of ladder-climbing exercise training on neurobiological markers in the hippocampus of mice with type 2 diabetes (T2DM). Twenty-one C57BL/6 male mice were randomly assigned to the non-diabetic control (NDC, n = 7), diabetic control (DC, n = 7), and diabetic training (DT, n = 7) groups. The DT group performed ladder-climbing training (LCT) five times a week for eight weeks. We measured the levels of hippocampal neurobiological markers (catalase [CAT], brain-derived neurotrophic factor [BDNF], nerve growth factor [NGF], amyloid-beta [Aβ], tau, and CC motif chemokine ligand 11 [CCL11]). The BDNF levels were significantly higher in the DT group than in the DC group (p < 0.05). The Aβ and CCL11 levels were significantly higher in the DC group than in the NDC and DT groups (p < 0.05). The tau levels were significantly higher in the DC group than in the NDC group (p < 0.05). However, there was no significant difference in CAT and NGF levels among the groups (p > 0.05). These results suggest that while T2DM could induce neurodegeneration, LCT may be effective in alleviating neurodegeneration caused by T2DM.

• BMB Reports
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• v.45 no.10
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• pp.583-588
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• 2012

Leukotactin(Lkn)-1 is a CC chemokine and is upregulated in macrophages in response to Mycobacterium tuberculosis (MTB) infection. We investigated whether mitogen-activated protein kinases (MAPKs) are involved in MTB-induced expression of Lkn-1. The up-regulation of Lkn-1 by infection with MTB was inhibited in cells treated with inhibitors specific for JNK (SP600125) or p38 MAPK (SB202190). Since the up-regulation of Lkn-1 by MTB has been reported to be mediated by the PI3-K/PDK1/Akt signaling, we examined whether JNK and/or p38 MAPK are also involved in this signal pathway. MTB-induced Akt phosphorylation was blocked by treatment with JNK- or p38 MAPK-specific inhibitors implying that p38 and JNK are upstream of Akt. In addition, treatment with the PI3-K-specific inhibitor inhibited MTB-stimulated activation of JNK or p38 MAPK implying that PI3-K is upstream of JNK and p38 MAPK. These results collectively suggest that JNK and p38 MAPK are involved in the signal pathway responsible for MTB-induced up-regulation of Lkn-1.

• The Journal of Internal Korean Medicine
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• v.25 no.4
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• pp.289-299
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• 2004

Background : Although the pathophysiology of asthma has been reported, its mechanism has not been fully elucidated. The mast cell is an effector cells in allergic inflammation and secretes a number of chemokines. Chemokines are important for the recruitment of leukocytes to sites of infection, which is essential in host defense. Chemokines also contribute to the pathogenesis of several disorders such as asthma, chronic bronchitis, atopic dermatitis, allergic rhinitis, and rheumatoid arthritis. Objective : In this study, the aim was to identify the effect of Baekryunchihyo-tang(白蓮治哮湯) on expression of chemokines. This was examined by RT-PCR using the human mast cell line (HMC-l) Materials and Methods : HMC-l cells were used, which is known to secrete and express chemokines. In order to investigate the protective effect of Baekryunchihyo-tang(白蓮治哮湯), HMC-l cells were incubated with pretreatment of Baekryunchihyo-tang(白蓮治哮湯) for 24 hrs. RT-PCR analyses of chemokine genes of cells pretreated with Baekryunchihyo-tang(白蓮治哮湯) showed that expressions of IL-8, $MIP-l{\beta}$, and RANTES genes in these cells were lower and $MIP-l{\alpha}$ showed a similar pattern compared to the calcium ionophore-treated group. In addition, cell cytotoxicity concentration measurements were performed by MTT assay method. Results : After stimulation with 1 uM calcium ionophore A23178 for 2 hrs, IL-8, major one of CXC chemokines, was highly expressed, and expression of $MIP-l{\beta}$ and RANTES (CC chemokines) increased, while expression of $MIP-l{\alpha}$ did not change. The cell cytotoxicity of Baekryunchihyo-tang(白蓮治哮湯) with treatments at various concentrations and times was not observed, respectively. Conclusion : This study suggests that Baekryunchihyo-tang(白蓮治哮湯) has dose-dependent effects on mRNA expression of IL-8(CXC chemokines), $MIP-l{\beta}$ and RANTES(CC chemokines) in human mast cellline(HMC-l). So these herbal medicines may inhibit the inflammatory process of asthma. Advanced studies are required to investigate the mechanism of inhibition by herbal medicine in the asthma model. This study provides basic data on the possibility of the clinical treatment of Baekryunchihyo-tang(白蓮治哮湯) for allergic disorders.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.898-908
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• 2000

Background : Eotaxin a CC chemokine specific for eosinophils, is implicated in the pathogenesis of asthma by recruiting eosinophils into the airways. Theophylline has been used for the treatment of asthma and recently was proposed to have an anti-inflammatory action. The aim of this study is to examine whether theophylline may inhibit the eosinophilic airway inflammation by reducing the expression of eotaxin. Methods : The expression of eotaxin mRNA was assessed by Northern analysis in A549 cells 4 h after stimulation with TNF-$\alpha$ or IL-1$\beta$. And then, theophylline was added to A549 cells stimulated with 0.1 ng/mL IL-1$\beta$. Results : Eotaxin mRNA expression rates induced by 0.1, 1, 10 ng/mL TNF-$\alpha$ as compared with $\beta$-actin, were 7%, 22%. 28%, respectively. Eotaxin mRNA expression rates induced by 0.01, 0.1, 1, 10 ng/mL IL-1$\beta$, as compared with $\beta$-actin, were 10%, 42%, 63%, 72%, respectively. Eotaxin mRNA expression rates after the addition of 0, 0.001, 0.01, 0.1 ${\mu}M$ dexamethasone induced by 10 ng/mL TNF-$\alpha$ as compared with $\beta$-actin, were 27%, 18%, 8%, respectively. Eotaxin mRNA expression rate after the addition of 0, 0.001, 0.01, 0.1 ${\mu}M$ dexamethasone induced by 0.1 ng/mL IL-1$\beta$ as compared with $\beta$-actin, were 43%, 47%, 12%, 8%, respectively. Eotaxin mRNA expression rates after the addition of 0, 0.001, 0.01, 0.1, 1, 10 mM theophylline induced by 0.1 ng/mL IL-1$\beta$, as compared with $\beta$-actin, were 48%, 40%, 33%, 22%, 16%, 14%, respectively. Conclusion : These results suggest that theophylline may reduce eosinophil infiltration of the airway at least in part by reducing the expression of eotaxin under the conditions of these experiments.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.416-423
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• 2023

Figs has known to have antioxidant, whitening, anti-inflammatory, and antibacterial effects in their leaves, roots, stems, latex, and fruits. In order to develop cosmetic materials based on natural products, we have studied on the skin activity of the ficin in latex as well as the whitening function of the fruit extract with 70% ethanol, and used it as a raw material for released cosmetic product. However, there is little research on the demand for the development of new eutectic solvent extraction methods and its ability to control skin inflammation and psoriasis regulation. Thus, in this study, we evaluated the effectiveness of fig fruit extracts and fractions using eutectic solvent extraction for skin inflammation control and psoriasis. First, fig fruits were extracted under optimal eutectic solvent conditions and fractionated with n-hexane, dichloromethane, ethyl acetate, and butanol. First, the antioxidant activity and inhibition of nitric oxide (NO) production were confirmed in mouse macrophage RAW264.7 cells. In addition, as a result of observing the mRNA expression through RT-PCR, pro-inflammatory cytokines such as TNF-α, IL1α, and IL-1β were suppressed significantly in the hexane, dichloromethane, and ethyl acetate fractions. In addition, it was confirmed in TNF-α stimulated HaCaT keratinocyte model. Finally, chemokine CC motif ligand 20 (CCL20), marker gene of human psoriasis skin disease, was significantly suppressed in the hexane, dichloromethane, and ethyl acetate fractions. These results suggested its anti-inflammatory and skin soothing effect and the possibility of development as an excellent skin soothing natural cosmetic material in the future through future clinical trials.

• International Journal of Oral Biology
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• v.44 no.4
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• pp.173-181
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• 2019

The CC chemokine receptor 5 (CCR5) is a G protein-coupled receptor that regulates chemotaxis and effector functions of immune cells. It also serves as the major co-receptor for the entry of human immunodeficiency virus (HIV). Recently, CCR5 inhibitors have been developed and used for the treatment or prevention of HIV infections. Additionally, it has been identified that CCR5 controls bone homeostasis by regulating osteoclastogenesis and the communication between osteoblasts and osteoclasts. However, the effects of CCR5 inhibition on bone tissue in elderly patients are unknown. This study aimed to examine the bone phenotype of aged CCR5 knockout (KO) mice. Femoral and tibial bones were isolated from 12-month and 18-month old wild-type (WT) and CCR5 KO mice, and microcomputed tomography and histology analyses were performed. Twelve-month-old CCR5 KO mice exhibited a decreased trabecular bone mass and cortical bone thickness in both femoral and tibial bones compared with age-matched WT mice. Eighteen-month-old mice also showed a decreased trabecular bone mass in femurs compared with control WT mice, but not in tibial bones. Unlike in 12-month-old mice, the cortical margin of femurs and tibias in 18-month-old mice were rough, likely because they were aggravated by the deficiency of CCR5. Overall, our data suggest that the deficiency of CCR5 with aging can cause severe bone loss. When CCR5 inhibitors or CCR5 inactivating technologies are used in elderly patients, a preventive strategy for bone loss should be considered.

• Tuberculosis and Respiratory Diseases
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• v.87 no.1
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• pp.65-79
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• 2024

Background: Exhaled condensates contain inflammatory biomarkers; however, their roles in the clinical field have been under-investigated. Methods: We prospectively enrolled subjects admitted to pulmonology clinics. We collected exhaled breath condensates (EBC) and analysed the levels of six and 12 biomarkers using conventional and multiplex enzyme-linked immunosorbent assay, respectively. Results: Among the 123 subjects, healthy controls constituted the largest group (81 participants; 65.9%), followed by the preserved ratio impaired spirometry group (21 patients; 17.1%) and the chronic obstructive pulmonary disease (COPD) group (21 patients; 17.1%). In COPD patients, platelet derived growth factor-AA exhibited strong positive correlations with COPD assessment test (ρ=0.5926, p=0.0423) and COPD-specific version of St. George's Respiratory Questionnaire (SGRQ-C) score (total, ρ=0.6725, p=0.0166; activity, ρ=0.7176, p=0.0086; and impacts, ρ=0.6151, p=0.0333). Granzyme B showed strong positive correlations with SGRQ-C score (symptoms, ρ=0.6078, p=0.0360; and impacts, ρ=0.6007, p=0.0389). Interleukin 6 exhibited a strong positive correlation with SGRQ-C score (activity, ρ=0.4671, p=0.0378). The absolute serum eosinophil and basophil counts showed positive correlations with pro-collagen I alpha 1 (ρ=0.6735, p=0.0164 and ρ=0.6295, p=0.0283, respectively). In healthy subjects, forced expiratory volume in 1 second (FEV₁)/forced vital capacity demonstrated significant correlation with CC chemokine ligand 3 (CCL3)/macrophage inflammatory protein 1 alpha (ρ=0.3897 and p=0.0068). FEV₁ exhibited significant correlation with CCL11/eotaxin (ρ=0.4445 and p=0.0017). Conclusion: Inflammatory biomarkers in EBC might be useful to predict quality of life concerning respiratory symptoms and serologic markers. Further studies are needed.