• The Korean Journal of Physiology and Pharmacology
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• v.23 no.2
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• pp.151-159
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• 2019

Pruritus (itching) is classically defined as an unpleasant cutaneous sensation that leads to scratching behavior. Although the scientific criteria of classification for pruritic diseases are not clear, it can be divided as acute or chronic by duration of symptoms. In this study, we investigated whether skin injury caused by chemical (contact hypersensitivity, CHS) or physical (skin-scratching stimulation, SSS) stimuli causes initial pruritus and analyzed gene expression profiles systemically to determine how changes in skin gene expression in the affected area are related to itching. In both CHS and SSS, we ranked the Gene Ontology Biological Process terms that are generally associated with changes. The factors associated with upregulation were keratinization, inflammatory response and neutrophil chemotaxis. The Kyoto Encyclopedia of Genes and Genomes pathway shows the difference of immune system, cell growth and death, signaling molecules and interactions, and signal transduction pathways. Il1a, Il1b and Il22 were upregulated in the CHS, and Tnf, Tnfrsf1b, Il1b, Il1r1 and Il6 were upregulated in the SSS. Trpc1 channel genes were observed in representative itching-related candidate genes. By comparing and analyzing RNA-sequencing data obtained from the skin tissue of each animal model in these characteristic stages, it is possible to find useful diagnostic markers for the treatment of itching, to diagnose itching causes and to apply customized treatment.

• Pediatric Infection and Vaccine
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• v.26 no.1
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• pp.51-59
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• 2019

Purpose: The aim of this study was to evaluate the relationships between cytokine and chemokine levels and the clinical severity of Mycoplasma pneumoniae pneumonia. Methods: A retrospective analysis of clinical and laboratory parameters were performed. Serum levels of interleukin (IL)-6, IL-8, IL-10, IL-18, interferon-${\gamma}$-inducible protein-10 (IP-10), macrophage inflammatory $protein-1{\beta}$, and tumor necrosis $factor-{\alpha}$ were measured. The severity of patients' clinical course and radiologic findings were also assessed. Results: Seventy-two patients (35 males and 37 females) with a median age of 3.9 years (range, 1-16 years) were enrolled. Patients with lobar pneumonia (n=29) had significantly higher C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and IL-18 values than those with broncho-interstitial pneumonia (n=43). However, the cytokine and chemokine values did not differ between the group that was treated with corticosteroids (n=31) and the one that was not (n=41). The CRP, ESR, lactate dehydrogenase (LDH), IL-18, and IP-10 values showed positive correlations with fever duration prior to admission. The CRP and ESR values were positively correlated with IL-18, and LDH, with IP-10 levels. Conclusions: CRP, ESR, LDH, IL-18, and IP-10 values were associated with the severity of the disease, manifesting lobar pneumonia or prolonged fever duration prior to admission.

• Korean Journal of Pharmacognosy
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• v.50 no.3
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• pp.219-225
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• 2019

This study was done to examine immunomodulative effects of aged doraji (AD) in the immune-suppressed mice induced by cyclophosphamide. The immune-stimulating effects of ethanol AD extract in in vivo at 75 and 150 mg/kg body weight (BW) for AD and 2AD groups were evaluated and compared to the normal doraji group (2ND, 150 mg/kg BW) treated with a doraji without aging process. After the 10 days of oral supplement, body and immune related organ weights, serum immunoglobulin G (IgG) and cytokines levels, splenocytes proliferation rate, and splenic NK cell activity were measured as immune-related biomarkers. Body weight and serum IgG level increased in the 2AD group. But, the serum Th2 cytokine (IL-6, $TNF-{\alpha}$) levels were lower in the AD and 2AD groups, respectively. Splenic T cell and B cell proliferation and NK cell activity increased in the doraji groups and the significant increases were found only in the 2AD group. Thus, the aged doraji extract may affect body weight, serum IgG level, splenocytes proliferation, and splenic NK cell activity, and normalize the Th2 cytokine levels in the immune-suppressed mice. The results suggest that the aged doraji improves effectively immune system rather than the normal one.

• Journal of Life Science
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• v.29 no.2
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• pp.256-264
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• 2019

Lymphotoxin ${\beta}$ receptor ($LT{\beta}R$), a member of the tumor necrosis factor receptor family, plays an important role in lymphoid tissue's architecture and organogenesis. In contrast, MLCK and ROCK play critical roles in the regulation of stress fiber (SF) formation in cells. To determine whether $LT{\beta}R$ stimulation in fibroblastic reticular cells (FRCs) is involved in these signaling pathways, myosin light chain kinase inhibitor-7 (ML-7) was used to inhibit them. ML7-treated FRCs completely blocked SFs and showed retraction and shrinkage processes comparable to those observed in agonistic anti-$LT{\beta}R$ antibody-treated cells. The inhibition of ROCK activity with Y27632-induced changes in actin cytoskeleton organization and cell morphology in FRCs. Actin bundles rearranged into SFs, and phospho-myosin light chain (p-MLC) co-localized in FRCs. We checked the level of Rho-guanosine diphosphate (RhoGDP)/guanosine triphosphate (GTP) exchange activity using FRC lysate. When $LT{\beta}R$ was stimulated with agonistic anti-$LT{\beta}R$ antibodies, Rho-GDP/GTP exchange activity was markedly reduced. Regarding $LT{\beta}R$ signaling with a focus on MLCK inhibition, we showed that the phosphorylation of MLCs was reduced by $LT{\beta}R$ stimulation in FRCs. Cytoskeleton components, such as tubulin, b-actin, and phospho-ezrin proteins acting as membrane-cytoskeleton linkers, were produced in de-phosphorylation, and they reduced expression in agonistic anti-$LT{\beta}R$ antibody-treated FRCs. Collectively, the results suggested that MLCK and ROCK were simultaneously responsible for SF regulation triggered by $LT{\beta}R$ signaling in FRCs.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.6
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• pp.348-354
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• 2020

Oryeong-san (ORS) is a traditional Korean herbal medicine widely used for renal associated diseases, composed of five medicine herbs; Atractylodes japonica Koidzumi, Cinnamomum cassia Presl, Polyporus umbellatus Fries, Poria cocos Wolf and Alisma orientale Juzepzuk. We studied to improve the convenience of intake and portability by developing modernized dosage forms, and examined the effect on anti-inflammation of ORS. In order to develop the tablet formulation of ORS (ORS-F), the tablets were evaluated on the basis of physical characteristics include diameter, thickness, weight variation, hardness, friability and disintegration. To analyze the marker components of ORS-F, eight index markers from five herbal medicines were chosen. And the method using high performance liquid chromatography (HPLC) with diode-array detector method was established for the simultaneous analysis. The biological activities were examined the effect of ORS-F on pro-inflammation mediated by LPS-stimulation. The production of nitric oxide (NO) and cytokines were determined by reacting cultured medium with griess reagent and enzyme-linked immunosorbent assay (ELISA). The expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) were investigated by Western blot and RT-PCR. The anti-oxidant activities of OJS-F increased markedly, in a dose-dependent manner. and, The total phenolic compound and flavonoids contents of OJS-F were 10.20±0.09 ㎍/㎎ and 12.86±0.86 ㎍/㎎. OJS-F which is LPS has diminished in the LPS-induced release of inflammatory mediators (NO, iNOS, COX2 and PGE2) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) from the RAW264.7 macrophages. Therefore, the developed formulation for tablet of ORS-F provide efficiency and usability, and indicated effect of anti-inflammation.

• Journal of Applied Biological Chemistry
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• v.65 no.2
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• pp.113-120
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• 2022

We examined the anti-inflammatory properties of Nostoc commune HCW0811 in lipopolysaccharide-stimulated RAW264.7 macrophage cells. The anti-inflammatory activity of HCW0811 on viability of treated cells was assessed by measuring the level of expression of NO, prostaglandin E₂ and pro-inflammatory cytokines, namely interleukin-1β, interleukin-6, and tumor necrosis factor-α in HCW0811 treated RAW 264.7 macrophages. HCW0811 was non-toxic to cells and inhibited the production of cytokines in a concentration-dependent manner. In addition its treatment suppressed the production of pro-inflammatory cytokines in a dose-dependent manner, and concomitantly decreased the protein expressions of inducible NO synthase and cyclooxygenase-2. Moreover, the levels of the phosphorylation of mitogen-activated protein kinase family proteins such as extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and nuclear factor kappa B were reduced by HCW0811. These findings suggest that the HCW0811 collected from Daejeon National Cemetery have anti-inflammatory effects, and demonstrated its efficacy in cell-based in vitro assays.

• The Korean Journal of Food And Nutrition
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• v.36 no.1
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• pp.6-16
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• 2023

To investigate the anti-inflammatory activity of submerged culture using Cordyceps militaris mycelium, culture-including mycelia was extracted and lyophilized into postbiotics (hot-water extract; CM-HW). HW was fractionated into crude polysaccharide (CM-CP) by ethanol precipitation, and CM-CP was further dialyzed into CM-DCP by dialysis with running water using 12~14 kDa dialysis tube. When the cytotoxicity of subfractions against cells was assessed, no subfraction had a cytotoxic impact that was substantially different from the control groups. In an inflammatory model using LPS-stimulated RAW 264.7 cells, CM-DCP significantly decreased IL-6 and MCP-1 production levels compared to the LPS-control group. CM-DCP also inhibited IL-6 and IL-8 secretion in HaCaT keratinocytes stimulated with TNF-α and IFN-γ. In the meanwhile, the neutral sugar content and mannose ratio of anti-inflammatory CM-DCP were higher than the other fractions, and CM-DCP contained β-1,3/1,6-glucan of 216.1 mg/g. High pressure size exclusion chromatography revealed that CM-DCP contained molecules with a molecular weight range of 5.6 to 144.0 kDa. In conclusion, postbiotics of C. militaris mycelium significantly promoted anti-inflammatory activity, suggesting that neutral polysaccharides including Glc and Man contribute to the anti-inflammation in RAW 264.7 or HaCaT cells.

• Journal of Marine Bioscience and Biotechnology
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• v.15 no.1
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• pp.1-11
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• 2023

In the present study, the antioxidant and anti-inflammatory activities of ethanolic extracts from Lathyrus japonicus at concentrations of 50, 100, and 200 ㎍/mL were investigated in LPS-stimulated, RAW264.7 cells. Antioxidant properties were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays and ferric reducing antioxidant power assay. In addition, the production of reactive oxygen species (ROS) was measured using the 2',7'-dichlorofluorescein diacetate (DCFH-DA) probe by flow cytometry. To examine the anti-inflammatory activity of the extracts of L. japonicus, their effects on the levels of nitric oxide (NO); production of cytokines such as interleukin (IL)-1β, IL-10, and tumor necrosis factor-α (TNF-α); and the activities of enzymes such as inducible NOS (iNOS) and cyclooxygenase-2 (COX-2) were assessed. The IC₅₀ values of the DPPH and ABTS radical scavenging assays were 476.09 ± 1.50 and 34.91 ± 0.37 ㎍/mL, respectively. In addition, L. japonicus extracts not only inhibited ROS production, but also the production of NO, IL-1β, and IL-10, and the activity of iNOS in a dose-dependent manner. In summary, the ethanolic extracts of L. japonicus could be used as a functional food additive and an anti-inflammatory agent owing to their antioxidant and anti-inflammatory activities

• Journal of Nutrition and Health
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• v.56 no.6
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• pp.615-628
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• 2023

Purpose: Increasing levels of domestic fine dust (DFD) have emerged as a serious problem that threatens public health by causing chronic respiratory diseases and skin aging. The present study was performed to investigate the inhibitory effects of Gryllus bimaculatus (the two-spotted cricket), which has recently attracted attention as an edible insect in South Korea, on DFD-induced aging and inflammation. Methods: To verify that DFD causes skin aging and investigate the anti-aging effect of an aqueous ethanolic-Gryllus bimaculatus extract (AE-GBE), human diploid fibroblasts (HDF) were treated with 100 ㎍/mL of European reference material (ERM)-CZ100 dust for 24 hrs in the presence or absence of 100 ㎍/ml AE-GBE. Aging and cellular toxicities were assessed by measuring reactive oxygen species (ROS) levels, DNA fragmentation, and β-galactosidase activity. The protein levels of cyclooxygenase (COX) 2, matrix metalloproteinase (MMP)-1, and collagen were measured by western blot, and the mRNA expressions of inflammation-related genes were assayed by quantitative reverse transcriptase polymerase chain reaction. Results: Treatment with ERM-CZ100 induced an aged phenotype in HDF cells, as evidenced by increased ROS levels, DNA fragmentation, and senescence-associated β-galactosidase activity, but cotreatment with AE-GBE significantly reduced these inductions. The mRNA expressions of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, induced by ERM-CZ100 were also reduced by AE-GBE cotreatment, which also reduced COX2 expression. Moreover, ERM-CZ100-induced MMP-1 expression and reduced collagen type I expression were recovered by AE-GBE treatment. Conclusion: These results suggest that AE-GBE is a potential treatment for domestic fine dust-induced skin inflammation and inflammaging.

• IMMUNE NETWORK
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• v.24 no.2
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• pp.3.1-3.23
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• 2024

Cigarette smoke extract (CSE)-treated mouse airway epithelial cells (MAECs)-derived exosomes accelerate the progression of chronic obstructive pulmonary disease (COPD) by upregulating triggering receptor expressed on myeloid cells 1 (TREM-1); however, the specific mechanism remains unclear. We aimed to explore the potential mechanisms of CSE-treated MAECs-derived exosomes on M1 macrophage polarization and pyroptosis in COPD. In vitro, exosomes were extracted from CSE-treated MAECs, followed by co-culture with macrophages. In vivo, mice exposed to cigarette smoke (CS) to induce COPD, followed by injection or/and intranasal instillation with oe-TREM-1 lentivirus. Lung function and pathological changes were evaluated. CD68⁺ cell number and the levels of iNOS, TNF-α, IL-1β (M1 macrophage marker), and pyroptosis-related proteins (NOD-like receptor family pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-1 recruitment domain, caspase-1, cleaved-caspase-1, gasdermin D [GSDMD], and GSDMD-N) were examined. The expression of maternally expressed gene 3 (MEG3), spleen focus forming virus proviral integration oncogene (SPI1), methyltransferase 3 (METTL3), and TREM-1 was detected and the binding relationships among them were verified. MEG3 increased N6-methyladenosine methylation of TREM-1 by recruiting SPI1 to activate METTL3. Overexpression of TREM-1 or METTL3 negated the alleviative effects of MEG3 inhibition on M1 polarization and pyroptosis. In mice exposed to CS, EXO^-CSE further aggravated lung injury, M1 polarization, and pyroptosis, which were reversed by MEG3 inhibition. TREM-1 overexpression negated the palliative effects of MEG3 inhibition on COPD mouse lung injury. Collectively, CSE-treated MAECs-derived exosomal long non-coding RNA MEG3 may expedite M1 macrophage polarization and pyroptosis in COPD via the SPI1/METTL3/TREM-1 axis.