• Journal of Nutrition and Health
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• v.36 no.9
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• pp.908-917
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• 2003

It has been proposed that oxidative modification of LDL (oxLDL) plays a significant role in the pathogenicity of atherogenesis. We tested the hypothesis that chitin and chitosan may function as antioxidants with respect to 0.1 mg cholesterol/ml LDL incubated with 5 $\mu$ M Cu$^2$$^{+}$alone or in the P338Dl mouse macrophage system using L-ascorbic acid as a standard classical antioxidant. The degree of oxLDL formation was ascertained by the relative electrophoretic mobility (rEM) in the combination of thiobarbituric acid reactive substances (TBARS) levels, and the cytotoxicity of oxLDL was detected by macrophage viability. The oxLDL uptake and foam cell formation of macrophages were measured by Oil Red O staining. Incubation with Cu$^2$$^{+}$and macrophages increased rEM of LDL and stimulated TBARS formation. Culture of macrophages with LDL in the presence 5 $\mu$ M Cu$^2$$^{+}$induced macrophage death. In cell-free system 200 $\mu$g/ml water-soluble chitosan and chitosan-oligosaccharide blocked oxLDL formation. Water-soluble chitosan and chitosan-oligosaccharide blocked oxLDL formation near-completely relative to L-ascorbic acid, whereas water-soluble chitin and chitin-oligosaccharide had no measurable antioxidant effect. In macrophage system water-soluble chitosan and chitosan-oligosaccharide blocked oxidation of LDL with a significant increase in cell viability, and decreased TBARS in medium. As for the inhibitory effect on macrophage foam cell formation, chitosan and its oligosaccharide, but not watersoluble chitin, revealed the effectiveness. The endothelial expression of lectin-like oxLDL receptor-1 (LOX-1) was tested by Western blot analysis, and chitosan, chitosan-oligosaccharide and chitin-oligosaccharide blocked LOX-1 expression. These results indicate that water-soluble chitosan and its oligosaccharide showed the inhibitory effect on Cu$^2$$^{+}$-induced LDL oxidation of macrophages, and chitosan, chitosan-oligosaccharide and chitin-oligosaccharide had blocking effect on oxLDL receptor expression in the human umbilical vein endothelial system. Thus, water-soluble chitosan and its oligosaccharides possess anti-atherogenic potentials possibly through the inhibition of macrophage LDL oxidation or endothelial oxLDL receptor expression depending on chemical types.l types.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.42
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• pp.23.1-23.11
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• 2020

Background: 4-Hexylresorcinol (4HR) is able to increase angiogenesis. However, its molecular mechanism in the human endothelial cells has not been clarified. Methods: As endothelial cells are important in angiogenesis, we treated the human umbilical vein endothelial cells (HUVECs) with 4HR and investigated protein expressional changes by immunoprecipitation high-performance liquid chromatography (IP-HPLC) using 96 antisera. Results: Here, we found that 4HR upregulated transforming growth factor-β (TGF-β)/SMAD/vascular endothelial growth factor (VEGF) signaling, RAF-B/ERK and p38 signaling, and M2 macrophage polarization pathways. 4HR also increased expression of caspases and subsequent cellular apoptosis. Mechanistically, 4HR increased TGF-β1 production and subsequent activation of SMADs/VEGFs, RAF-B/ERK and p38 signaling, and M2 macrophage polarization. Conclusion: Collectively, 4HR activates TGF-β/SMAD/VEGF signaling in endothelial cells and induced vascular regeneration and remodeling for wound healing.

• Journal of Digital Convergence
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• v.17 no.5
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• pp.399-405
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• 2019

This study was investigated the effect of aerobic exercise and chrysin supplementation on macrophage infiltration and lipolysis in high-fat diet mice. To accomplish the purpose of this study, C57BL/6 mice were fed high fat diet(60% fat diet) during experimental period. The animals were divided into 4 groups; NC (normal diet control, n=5), HC (high fat diet control, n=5), Hch(high fat diet with chrysin, n=5), and HME (high fat diet with aerobic exercise training, n=5). Exercise training was performed for 16 weeks on a treadmill running. As a result, macrophage marker, F480 and CD11c were significantly decreased in HME comparison with HD and Hch. Also, M2 macrophage marker CD11c, and lipolysis marker PRDM were significantly increased in HME compared with HC and Hch These findings suggest that regular aerobic exercise has beneficial effects to inhibit macrophage infiltration in high fat diet mice.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.6
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• pp.1514-1518
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• 2003

Angelica sinensis radix, Danggui, is a traditional oriental medication, which has been used to modulate immune response. We report here that aqueous extract of Angelica sinensis radix (ASR) can induces NO production, and inhibit LPS-induced NO production in dose-dependent manner in RAW 264.7 macrophage cells. ASR also induces iNOS mRNA and iNOS protein expression, and exhibit inhibitory effect on iNOS mRNA and protein expression in a dose-dependent manner in LPS-stimulated RAW 264.7 macrophage cells. Cytokines involved in the regulation of inflammatory reaction and immune response may play a role in the pathogenesis. ASR induces. pro-inflammatory cytokine gene expression (IL-1α, IL-1β and IL-6 gene) in a dose-dependent manner, and inhibits the expressions of these cytokines in LPS-stimulated RAW 264.7 macrophage cells. These data indicate that (1) ASR may be a potential therapeutic modulator of NO synthesis in various pathological conditions, and (2) the immunomodulatory effects of ASR may be, in part, associated with the inducing or suppression of pro-inflammatory cytokine gene expressions.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.154-165
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• 2021

This study aimed to investigate whether the antidiabetic drugs dipeptidyl peptidase 4 (DPP4) inhibitors such as evogliptin and sitagliptin affect the membrane DPP4 (mDPP4) enzymatic activity and immune function of T helper1 (Th1) cells in terms of cytokine expression and cell profiles. The mDPP4 enzymatic activity, cytokine expression, and cell profiles, including cell counts, cell viability, DNA synthesis, and apoptosis, were measured in pokeweed mitogen (PWM)-activated CD4+CD26+ H9 Th1 cells with or without the DPP4 inhibitors, evogliptin and sitagliptin. PWM treatment alone strongly stimulated the expression of mDPP4 and cytokines such as interleukin (IL)-2, IL-10, tumor necrosis factor-alpha, interferon-gamma, IL-13, and granulocyte-macrophage colony stimulating factor in the CD4+CD26+ H9 Th1 cells. Evogliptin or sitagliptin treatment potently inhibited mDPP4 activity in a dose-dependent manner but did not affect either the cytokine profile or cell viability in PWM-activated CD4+CD26+ H9 Th1 cells. These results suggest that, following immune stimulation, Th1 cell signaling pathways for cytokine expression function normally after treatment with evogliptin or sitagliptin, which efficiently inhibit mDPP4 enzymatic activity in Th1 cells.

• BMB Reports
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• v.56 no.6
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• pp.359-364
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• 2023

KAI1/CD82, a membrane tetraspanin protein, can prevent various cancers and retinal disorders through its anti-angiogenic and anti-metastatic capacity. However, little is known about its anti-inflammatory effect and molecular mechanism. Therefore, the present study aimed to inLPSvestigate effect of a recombinant protein of the large extracellular domain of human KAI1 (Gly 111-Leu 228, rhKAI1) on lipopolysaccharides (LPS)-stimulated RAW264.7 macrophage-like cells and mouse bone marrow-derived macrophages (BMDM) and to identify its underlying mechanism. Our data showed that rhKAI1 suppressed expression levels of classically macrophages (M1) phenotype-related surface markers F4/80+CD86+ in LPS-stimulated BMDM and RAW264.7 cells. In addition, LPS markedly increased mRNA expression and release levels of pro-inflammatory cytokines and mediators such as interleukin (IL)-1β, IL-6, tumor necrosis factor-α, cyclooxygenase-2, nitric oxide and prostaglandin E2, whereas these increases were substantially down-regulated by rhKAI1. Furthermore, LPS strongly increased expression of NF-κB p65 in the nuclei and phosphorylation of ERK, JNK, and p38 MAPK. However, nuclear translocation of NF-κB p65 and phosphorylation of JNK were greatly reversed in the presence of rhKAI1. Especially, rhKAI1 markedly suppressed expression of toll-like receptor (TLR4) and prevented binding of LPS with TLR4 through molecular docking predict analysis. Importantly, Glu 214 of rhKAI1 residue strongly interacted with Lys 360 of TLR4 residue, with a binding distance of 2.9 Å. Taken together, these findings suggest that rhKAI1 has an anti-inflammatory effect on LPS-polarized macrophages by interacting with TLR4 and down-regulating the JNK/NF-κB signaling pathway.

• BMB Reports
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• v.33 no.4
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• pp.308-311
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• 2000

The interrelationship between the differentiation and expression of mRNA for transferrin in the HL-60 leukemia cell line was studied. Transferrin mRNA was expressed in HL-60 leukemia cells and the amount was 50% of that in the positive control cell line, HepG-2 cells. The expression of $T_f$ mRNA in HL-60 cells was not regulated by IL-1, IL-6 and $TNF-{\alpha}$, respectively. The expression of $T_f$ mRNA in the differentiated cells into a granulocyte lineage by DMSO, or all-trans RA, was up-regulated (160-170% of control cells); whereas, the expression was not regulated in the differentiated cells into a macrophage lineage by PMA. These results suggest that the differentiation to a granulocyte lineage of HL-60 leukemia cells appear to be related with the upregulation of transferrin mRNA expression.

• Microbiology and Biotechnology Letters
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• v.48 no.3
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• pp.310-315
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• 2020

Orostachys japonicus (O. japonicus) is known as a medicinal plant for the treatment of various symptoms. This study investigated the anti-inflammatory effect of the hexane fraction from O. japonicus (OJH) on the LPS-stimulated response in RAW 264.7 macrophage cells. This study was conducted to confirm the effect of cell cytotoxicity and production of reactive oxygen species (ROS) in OJH-treated macrophage cells. Additionally, pro-inflammatory cytokines and transcription factors were determined using RT-PCR and western blotting assay. OJH showed no change in lactate dehydrogenase (LDH) levels and exhibited reduced ROS levels in LPS-induced inflammatory cells. Moreover, OJH significantly suppressed the mRNA levels of proinflammatory cytokines, including IL-1β, IL-2, IL-6, TNF-α, and IP-10. Furthermore, OJH effectively inhibited the protein levels of AP-1 (p-c-Jun and p-c-Fos) and p-IRF3 in a dose-dependent manner. In conclusion, our results demonstrate that OJH exhibits strong anti-inflammatory activities via regulation of inflammatory factors.

• Biotechnology and Bioprocess Engineering:BBE
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• v.9 no.1
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• pp.12-16
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• 2004

Partitioning of human granulocyte-macrophage colony stimulating factor (hGM-CSF) was achieved in the aqueous two-phase systems (ATPSs) using a crude extract of transgenic tobacco cell suspension culture. This study examined the effects of polyethylene glycol (PEG) molecular weight and concentration and the effects of sodium phosphate concentration in different PEG/sodium phosphate systems on the partition coefficient, K. The best ATPS system was 5% PEG 8,000/1.6 M sodium phosphate after 2 h of incubation at room temperature. In this system, hGM-CSF was partitioned in the PEG-rich phase with a yield of 57.99% and K$\_$hGM-CSF/ of 8.12. In another system, 3% PEG 10,000/1.6 M sodium phosphate, hGM-CSF was also partitioned primarily in the top phase with a yield of 45.66% and K$\_$hGM-CSF/ of 7.64 after 2 h of incubation at room temperature.

• Korean Journal of Pharmacognosy
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• v.32 no.3 s.126
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• pp.181-188
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• 2001

During the screening for inhibitors of nitric oxide production in LPS-activated macrophage, RAW 264.7 cells, two coumarins were isolated from chloroform extract of the root of Polygonum cuspidatum. They were identified as decursin (1) and decursinol angelate (2) on the basis of spectroscopic methods. The $IC_{50}$ values of these compounds on NO production were $0.76\;{\mu}M$ (1) and $2.6\;{\mu}M$ (2), respectively. However, the iNOS activity was not inhibited by treatment with these compounds. Their inhibitory effect on NO production seems to result from the suppression of iNOS induction through the suppression of NF-kB activity.