• Journal of Veterinary Science
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• 제24권4호
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• pp.52.1-52.13
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• 2023

Background: Mesenchymal stem cells (MSCs) have been investigated as therapeutic agents for inflammatory bowel disease (IBD). Stimulation of MSCs with pro-inflammatory cytokines is an approach to enhance their immunomodulatory effects. However, further investigation is required to support their application in immune-mediated disorders and companion animals. Objectives: This study aimed to assess the therapeutic effect of tumor necrosis factor (TNF)-α-stimulated feline adipose tissue-derived MSCs (fAT-MSCs) in a dextran sulfate sodium (DSS)-induced colitis mouse model. Methods: Colitis mice was made by drinking water with 3% DSS and fAT-MSCs were injected intraperitoneally. Colons were collected on day 10. The severity of the disease was evaluated and compared. Raw 264.7 cells were cultured with the conditioned medium to determine the mechanism, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Results: TNF-α-stimulated fAT-MSCs more improved severity of DSS-induced colitis in disease activity, colon length, histologic score, and inflammatory cytokine. In sectionized colon tissues, the group comprising TNF-α-stimulated fAT-MSCs had higher proportion of CD11b⁺CD206⁺ macrophages than in the other groups. In vitro, TNF-α-stimulation increased cyclooxygenase-2 (COX-2) expression and prostaglandin E₂ (PGE₂) secretion from fAT-MSCs. The conditioned medium from TNF-α-stimulated fAT-MSCs enhanced the expression of interleukin-10 and arginase-1 in LPS-activated Raw 264.7 cells. Conclusions: These results represent that TNF-α-stimulated fat-mscs ameliorate the inflamed colon more effectively. Furthermore, we demonstrated that the effectiveness was interlinked with the COX-2/PGE₂ pathway.

• Biomolecules & Therapeutics
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• 제22권1호
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• pp.55-61
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• 2014

Panax ginseng is a medicinal herb that is used worldwide. Its medicinal effects are primarily attributable to ginsenosides located in the root, leaf, seed, and flower. The flower buds of Panax ginseng (FBPG) are rich in various bioactive ginsenosides, which exert immunomodulatory and anti-inflammatory activities. The aim of the present study was to assess the effect of 18 ginsenosides isolated from steamed FBPG on the transcriptional activity of NF-${\kappa}B$ and the expression of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-stimulated target genes in liver-derived cell lines. Noticeably, the ginsenosides $Rk_3$ and $Rs_4$ exerted the strongest activity, inhibiting NF-${\kappa}B$ in a dose-dependent manner. SF and $Rg_6$ also showed moderately inhibitory effects. Furthermore, these four compounds inhibited the TNF-${\alpha}$-induced expression of IL8, CXCL1, iNOS, and ICAM1 genes. Consequently, ginsenosides purified from steamed FBPG have therapeutic potential in TNF-${\alpha}$-mediated diseases such as chronic hepatic inflammation.

• 한국임상수의학회지
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• 제25권6호
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• pp.440-446
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• 2008

Glucocorticoids (GCs) are the most widely used immunosuppressive agents, but animals treated with GCs may experience deleterious side effects which limit their use in many clinical conditions. In the present study, we examined whether methylprednisolone sodium succinate (MPSS), a glucocorticoid, modulates circulating leukocyte numbers, phagocytic capacity and oxidative burst activity (OBA) of canine peripheral blood phagocytes, and whether tumor necrosis factor-alpha (TNF-$\alpha$) release is affected by MPSS injection. Neutrophilia and monocytosis were induced by the administration of a high dose of MPSS, which is the recommended protocol for canine patients with acute spinal cord injury. The injection of MPSS decreased the phagocytic capacity of canine PMNs but not PBMCs, and recovered 12 hours (hr) after the completion of MPSS dosing. The OBA of both PMNs and PBMCs was suppressed by MPSS, and restored 24 hr after the completion of dosing. The lipopolysaccharide-induced TNF-α release by PBMCs but not PMNs exposed to MPSS was reduced 12 hr after the completion of dosing, and recovered 48 hr after the completion of dosing. These results suggest that the application of MPSS protocol inhibits the innate immune functions of canine peripheral blood phagocytes for short time relatively.

• Journal of Menopausal Medicine
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• 제24권3호
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• pp.169-175
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• 2018

Objectives: The rate of metabolic syndrome (MetS) in women diagnosed as they age is one of the main concerns of health cares. Recently new strategies used to prevent progressions of MetS toward the diagnosis of diabetes have focused on plant flavonoids. This study was aimed to investigate the beneficial effects of flavonoids fraction of Mespilus germanica leaves (MGL) on MetS in ovariectomized (OVX) rats. Methods: Twenty-four adult female Wistar rats, weighing 200 to 250 g, were divided into 3 groups: Sham surgery, OVX + Salin, or OVX + Flavonoid. Three weeks after ovariectomy, animals displayed MetS criteria received flavonoid injection (10 mg/kg, intraperitoneally) for 21 days. Then the body weight, body mass index, waist circumference, visceral fat, fasting blood glucose, serum insulin, lipid profiles and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) were measured. Results: Treatment with flavonoids fraction of MGL significantly decreased serum level of insulin (P = 0.011), glucose (P = 0.024), $TNF-{\alpha}$ (P = 0.010), also MetS Z score (P = 0.020) and homeostasis model assessment of insulin resistance (P = 0.007). Lipid profiles and visceral fat showed insignificant reduction. Conclusions: Flavonoids of MGL attenuates some of the MetS components possibly via reduction in $TNF-{\alpha}$ inflammatory cytokine.

• Journal of Veterinary Science
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• 제19권6호
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• pp.744-749
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• 2018

Dapsone, an antibiotic, has been used to cure leprosy. It has been reported that dapsone has anti-inflammatory activity in hosts; however, the anti-inflammatory mechanism of dapsone has not been fully elucidated. The present study investigated the anti-inflammatory effects of dapsone on bone marrow cells (BMs), especially upon exposure to lipopolysaccharide (LPS). We treated BMs with LPS and dapsone, and the treated cells underwent cellular activity assay, flow cytometry analysis, cytokine production assessment, and reactive oxygen species assay. LPS distinctly activated BMs with several characteristics including high cellular activity, granulocyte changes, and tumor necrosis factor alpha ($TNF-{\alpha}$) production increases. Interestingly, dapsone modulated the inflammatory cells, including granulocytes in LPS-treated BMs, by inducing cell death. While the percentage of Gr-1 positive cells was 57% in control cells, LPS increased that to 75%, and LPS plus dapsone decreased it to 64%. Furthermore, dapsone decreased the mitochondrial membrane potential of LPS-treated BMs. At a low concentration ($25{\mu}g/mL$), dapsone significantly decreased the production of $TNF-{\alpha}$ in LPS-treated BMs by 54%. This study confirmed that dapsone has anti-inflammatory effects on LPS-mediated inflammation via modulation of the number and function of inflammatory cells, providing new and useful information for clinicians and researchers.

• BMB Reports
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• 제40권2호
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• pp.290-294
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• 2007

Saxatilin is a disintegrin known to inhibit tumor progression in vivo and in vitro. The role of saxatilin in cancer cell invasion was examined by a modified Boyden chamber assay in MDAH 2774 human ovarian cancer cell line. Saxatilin (50 nM) significantly inhibited cancer cell invasion induced by tumor necrosis factor-$\alpha$ (TNF-a$\alpha$). Saxatilin also reduced MMP-9 mRNA levels in cancer cells in a dosedependent manner. In addition, TNF-$\alpha$-induced MMP-9 activity was reduced by the treatment of saxatilin. These results indicate that transcriptional regulation of MMP-9 is an important mechanism for the tumor suppressive effects of saxatilin in MDAH 2774 human ovarian cancer cells.

• 동의생리병리학회지
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• 제18권6호
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• pp.1805-1809
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• 2004

In order to validate the use of Radix Curcumae Aromaticae as an anti-inflammatory drug in the traditional Korean medicine, I have investigated the effect of water-soluble extract of Radix Curcumae Aromaticae (ECA) on the expression of inducible heme oxygenase-1 (HO-1), which ha.s anti-inflammatory and cytoprotective effects stimulates, in human umbilical vein endothelial cells (HUVECs) stimulated with a high dose of pro-inflammatory tumor necrosis factor-alpha (TNF-α). The extract protected dose-dependently HUVECs against TNF-α-induced apoptosis, as measured qualitatively by a nuclear staining method using the fluoresoence DAPI and quantitatively by a flow cytometry using fluoresce-enhanced Annexin V antibody, and significantly Increased HO-1 expression, as determined by Western blotting analysis using anti-HO-1 antibody. Biockage of HO-1 activity by a pharmacological inhibitor reversed cytoprotection afforded by the extract, and treatment with carbon monoxide, one of HO-1 metabolites, resulted in cytoprotection comparable to the extract. These results suggest that ECA may have therapeutic potential in the control of endothelial disorders caused by inflammatory cytokines.

• Restorative Dentistry and Endodontics
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• 제24권1호
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• pp.187-199
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• 1999

Bone remodeling is characterized by the continuing processes of osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Bone metabolism is tightly regulated at the local level by networks of hormones, cytokines, and other factors. In pathological conditions of bone remodeling, including osteoporosis and periodontal diseases, inflammatory cytokines and local mediators are responsible for enhancement of osteoclast resorption and inhibition of repair at the sites of bone resorption. TNF-${\alpha}$ is a pleiotropic hormone with actions on the differentiation, growth, and functional activities of normal and malignant cells from numerous tissues. TNF-${\alpha}$ has been proposed as a local mediator of the control of bone turnover in situations of chronic inflammation, and it has been assumed that the local source of TNF-${\alpha}$ is the monocyte in the adjacent bone marrow or the local circulation. TNF-${\alpha}$ is a potent inducer of bone resorption. TNF-${\alpha}$ is known to induce the activation of apoptotic signaling pathway, which leads to the apoptosis of bone cells. We demonstrated that treatment of murine osteoblastic MC3T3E1 cells with TNF-${\alpha}$ decreases proliferation as well as alkaline phosphatase (ALP) activity in a dose depenent manner. In addition, TNF-${\alpha}$ increases osteoclast-like cell formation in $1{\alpha}$, 25(OH)2D3 or PGE2-treated bone marrow cell culture. When cells were cultured in TNF-${\alpha}$ free ${\alpha}$-MEM, this inhibitory effect of ALP activity was reversible up to 10 ng/ml TNF-${\alpha}$, in contrast, at the 20 ng/ml TNF-${\alpha}$, irreversible. In this concentration, TNF-${\alpha}$ may induce apoptosis in MC3T3E1 cells. In this study, TNF-${\alpha}$ induces apoptosis resulting in chromosomal DNA fragmentation, preceded by JNK/SAPKs and caspase-3 activation. Our present results show that JNK/SAPKs and caspase-3 are activated by TNF-${\alpha}$, suggesting that the JNK/SAPKs and caspase-3 participate in the bone resorption, associated with apoptosis.

• Journal of Applied Biological Chemistry
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• 제64권4호
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• pp.375-382
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• 2021

조록나무는 제주도 및 일본 혼슈 이남, 중국 동남부, 타이완 등에 분포하는 조록나무과의 상록 교목으로, 항산화 및 tyrosinase, elastase의 억제에 효과적인 것으로 알려져 있지만 NO에 대한 억제 효능은 미미한 것으로 보고되었다. 이에 본 연구는 조록나무 잎 추출물(DL)에 biorenovation 생물 전환 기법을 적용하여 항 염증 활성을 증진 시키고자 수행되었다. 이들의 활성은 LPS로 자극된 RAW264.7 염증 모델에서 평가 되었으며 NO, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) 및 전 염증성 사이토카인에 대한 억제 실험이 수행되었다. 그 결과, biorenovation을 적용한 조록나무 잎 추출물(DLB)는 독성이 없는 농도에서 DL대비 향상된 NO와 prostaglandin E2 억제효능을 나타내었으며, 이들의 합성 효소인 iNOS 및 COX-2의 발현에도 유의한 억제 경향을 나타내었다. 또한 대표적인 전 염증성 사이토 카인인 tumor necrosis factor-α, Interleukin 6, Interleukin-1β 에서도 향상된 억제 효능을 확인 하였다. 이러한 결과를 근거로 우리는 biorenovation을 통해 DL의 항염증 효능이 개선될 수 있으며, DLB가 효과적인 천연 항염증 소재로 적용될 수 있음을 제시한다.

• Journal of Animal Science and Technology
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• 제65권2호
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• pp.351-364
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• 2023

The experiment was carried out to study the effect of Korean wild ginseng adventitious root supplementation on the laying performance, egg quality, cytokine expression, ginsenoside concentration, and microflora quantity of Institut de selection Animale (ISA) brown laying hens at 24 weeks old. A total of 90 laying hens were subjected to a completely randomized design at three treatments, five repetitions and six laying hens per replicate. The experiments were divided by diets into the basic feed (CON), basic feed + 0.1% wild ginseng (WG1), and basic feed + 0.5% wild ginseng (WG2). The feeding trial was carried out over a duration of 12 weeks after an initial acclimation period of 2 weeks. Feeds and water were administered ad libitum in mash form, and light was available for 16 hours per day. At the end of study, henday egg production (HDEP), average egg weight (AEW), and egg mass (EM) were increased (p <0.05) in WG2 at week 12. Feed conversion ratio (FCR) was decreased (p < 0.05) in WG2 at week 12. The ginsenoside content in egg yolk was increased (p <0.05) in laying hens in the WG2 treatment at week 12. Relative expression of tumor necrosis factor alpha (TNF-α) was reduced (p < 0.05) in the WG supplemented diets at week 12. The fecal microflora quantity of Lactobacillus was increased (p < 0.05) in WG2 at week 8 to week 12, and Escherichia coli (E. coli) was significantly decreased (p < 0.05) in the WG2 at week 12. We concluded that the result observed in the HDEP, AEW, EM and FCR was due to an increase in ginsenoside content, leading to an improvement in the TNF-α, and fecal microflora quantity such as Lactobacillus and E. coli in the WG2 supplemented diets. We therefore recommend the use of WG at application level 0.5% per basal diet for optimum laying performance in layer hens.