• Biomedical Science Letters
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• v.12 no.3
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• pp.217-224
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• 2006

It has been reported that the dysfunctions of podocytes are associated with the development of diabetic nephropathy. In addition, insulin-like growth factors (IGFs) are associated with the development of diabetic nephropathy. However, it is not yet known about the effect of high glucose on IGF-I, -II secretion, and IGF binding proteins (IGFBPs) expression in the podocytes. Thus, this study was conducted to examine the effect of high glucose on IGF system and its involvement of protein kinase C (PKC) and mitogen activated protein kinases (MAPKs) in podocytes. In this study, high glucose (25 mM) increased IGF-I and IGF-II secretion (P<0.05), which was blocked by SB 203580 (a p38 MAPK inhibitor) but not by PD 98059 (a p44/42 MAPK inhibitor). In addition, high glucose-induced stimulation of IGFs was blocked by bisindolylmaleimide I and staurosporine (protein kinase C inhibitors). High glucose also increased IGFBP-l expression, which was blocked by bisindolylmaleimide I and SB 203580. In conclusion, high glucose alters IGFs secretion and IGFBP expression via PKC and p38 MAPK pathways in podocytes.

• Nutrition Research and Practice
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• v.13 no.4
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• pp.279-285
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• 2019

BACKGROUND/OBJECTIVES: Excessive production of reactive oxygen species (ROS) such as hydroxyl (${\cdot}OH$), nitric oxide (NO), and hydrogen peroxide ($H_2O_2$) is reported to induce oxidative stress. ROS generated by oxidative stress can potentially damage glial cells in the nervous system. Cordyceps militaris (CM), a kind of natural herb widely found in East Asia. In this study, we investigated the free radical scavenging activity of the CM extract and its neuroprotective effects in $H_2O_2$-induced C6 glial cells. MATERIALS/METHODS: The ethanol extract of CM ($100-1,000{\mu}g/mL$) was used to measure DPPH, ${\cdot}OH$, and NO radical scavenging activities. In addition, hydrogen peroxide ($H_2O_2$)-induced C6 glial cells were treated with CM at $0.5-2.5{\mu}g/mL$ for measurement of cell viability, ROS production, and protein expression resulting from oxidative stress. RESULTS: The CM extract showed high scavenging activities against DPPH, ${\cdot}OH$, and NO radicals at concentration of $1,000{\mu}g/mL$. Treatment of CM with $H_2O_2$-induced oxidative stress in C6 glial cells significantly increased cell viability, and decreased ROS production. Cyclooxygenase-2 and inducible nitric oxide synthase protein expression was down-regulated in CM-treated groups. In addition, the protein expression level of phospho-p38 mitogen-activated protein kinase (p-p38 MAPK), phospho-c-Jun N-terminal kinase (p-JNK), and phospho-extracellular regulated protein kinases (p-ERK) in $H_2O_2$-induced C6 glial cells was down-regulated upon CM administration. CONCLUSION: CM exhibited radical scavenging activity and protective effect against $H_2O_2$ as indicated by the increased cell viability, decreased ROS production, down-regulation of inflammation-related proteins as well as p-p38, p-JNK, and p-ERK protein levels. Therefore, we suggest that CM could play the protective role from oxidative stress in glial cells.

• Archives of Pharmacal Research
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• v.28 no.7
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• pp.784-790
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• 2005

In this study, we evaluate the effects of (-)-epigallocatechin-3-gallate (EGCG) on ultraviolet B(UVB)-irradiated living skin equivalents (LSEs). Histologically, UVB irradiation induced thinning of the LSE epidermis, whereas EGCG treatment led to thickening of the epidermis. Moreover, EGCG treatment protected LSEs against damage and breakdown caused by UVB exposure. Immunohistochemically, UVB-exposed LSEs expressed p53, Fas, and 8-hydroxy-deoxyguanosine (8-OHdG), all of which are associated with apoptosis. However, EGCG treatment reduced the levels of UVB-induced apoptotic markers in the LSEs. In order to determine the signaling pathways induced by UVB, Western blot analysis was performed for both c-Jun $NH_2$-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), which are associated with UVB-induced oxidative stress. UVB activated JNK in the epidermis and dermis of the LSEs, and EGCG treatment reduced the UVB-induced phosphorylation of JNK. In addition, p38 MAPK was also found to have increased in the UVB-exposed LSEs. Also, EGCG reduced levels of the phosphorylation of UVB-induced p38 MAPK. In conclusion, pretreatment with EGCG protects against UVB irradiation via the suppression of JNK and p38 MAPK activation. Our results suggest that EGCG may be useful in the prevention of UVB-induced human skin damage, and LSEs may constitute a potential substitute for animal and human studies.

• Clinical and Experimental Pediatrics
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• v.60 no.6
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• pp.181-188
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• 2017

Purpose: Hypoxic-ischemic encephalopathy is a significant cause of neonatal morbidity and mortality. Erythropoietin (EPO) is emerging as a therapeutic candidate for neuroprotection. Therefore, this study was designed to determine the neuroprotective role of recombinant human EPO (rHuEPO) and the possible mechanisms by which mitogen-activated protein kinase (MAPK) signaling pathway including extracellular signal-regulated kinase (ERK1/2), JNK, and p38 MAPK is modulated in cultured cortical neuronal cells and astrocytes. Methods: Primary neuronal cells and astrocytes were prepared from cortices of ICR mouse embryos and divided into the normoxic, hypoxia (H), and hypoxia-pretreated with EPO (H+EPO) groups. The phosphorylation of MAPK pathway was quantified using western blot, and the apoptosis was assessed by caspase-3 measurement and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Results: All MAPK pathway signals were activated by hypoxia in the neuronal cells and astrocytes (P<0.05). In the neuronal cells, phosphorylation of ERK-1/-2 and apoptosis were significantly decreased in the H+EPO group at 15 hours after hypoxia (P<0.05). In the astrocytes, phosphorylation of ERK-1/-2, p38 MAPK, and apoptosis was reduced in the H+EPO group at 15 hours after hypoxia (P<0.05). Conclusion: Pretreatment with rHuEPO exerts neuroprotective effects against hypoxic injury reducing apoptosis by caspase-dependent mechanisms. Pathologic, persistent ERK activation after hypoxic injury may be attenuateed by pretreatment with EPO supporting that EPO may regulate apoptosis by affecting ERK pathways.

• Molecules and Cells
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• v.38 no.1
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• pp.58-64
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• 2015

Activating transcription factor-3 (ATF3) acts as a negative regulator of cytokine production during Gram-negative bacterial infection. A recent study reported that ATF3 provides protection from Streptococcus pneumoniae infection by activating cytokines. However, the mechanism by which S. pneumoniae induces ATF3 after infection is still unknown. In this study, we show that ATF3 was upregulated via Toll-like receptor (TLR) pathways in response to S. pneumoniae infection in vitro. Induction was mediated by TLR4 and TLR2, which are in the TLR family. The expression of ATF3 was induced by pneumolysin (PLY), a potent pneumococcal virulence factor, via the TLR4 pathway. Furthermore, ATF3 induction is mediated by p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Thus, this study reveals a potential role of PLY in modulating ATF3 expression, which is required for the regulation of immune responses against pneumococcal infection in macrophages.

• Journal of Life Science
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• v.33 no.6
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• pp.463-470
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• 2023

Desmarestia tabacoides Okamura is a brown macroalgae that is found worldwide. Although several genera of Desmarestia have been reported as having anti-tumorigenic, anti-melanogenic, and photoprotective properties, the anti-inflammatory activity of D. tabacoides Okamura has not yet been evaluated. In this study, we analyzed the anti-inflammatory mechanisms of D. tabacoides Okamura ethanol extract (DTEE) via the inhibition of nitric oxide (NO) and prostaglandin (PG) E₂ production and the expression of their corresponding enzymes, inducible NO synthase (iNOS), and cyclooxygenase (COX)-2. In addition, their upstream signaling molecules were evaluated by Western blot analysis, such as nuclear factor (NF)-κB, mitogen-activated protein kinase (MAPK), and phosphoinositide-3-kinase (PI3K)/Akt, in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The DTEE treatment significantly inhibited LPS-induced NO and PGE₂ production as well as the expression of their corresponding enzymes, iNOS, and COX-2 without cytotoxicity. The stimulated transcription factor NF-κB and upstream signaling molecules extracellular signal-regulated kinase (ERK), c-Jun NH₂-terminal kinase (JNK), and p38 were attenuated by the DTEE treatment, which was statistically significant, while Akt did not provide any inhibitory effect. Moreover, the DTEE treatment significantly mitigated the LPS-activated adaptor molecules, toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) in the RAW 264.7 cells. These results suggest that DTEE attenuates TLR4-mediated inflammatory responses by inhibiting NF-κB activation and suppressing MAPK phosphorylation in LPS-stimulated RAW 264.7 cells.

• Clinical and Experimental Pediatrics
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• v.48 no.6
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• pp.580-587
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• 2005

New evidence is emerging that airway smooth muscle(ASM) may act as an immunomodulatory cell by providing pro-inflammatory cytokines and chemokines, polypeptide growth factors, extracellular matrix proteins, cell adhesion receptors and co-stimulatory molecules. ASM can promote the formation of the interstitial extracellular matrix, and potentially contribute to the alterations within the extracellular matrix in asthma. In addition, extracellular matrix components can alter the proliferative, survival, and cytoskeletal synthetic function of ASM cells through integrin-directed signaling. Increased ASM mass is one of the most important features of the airway wall remodeling process in asthma. Three different mechanisms may contribute to the increased ASM mass : cell proliferation, increased migration and decreased rate of apoptosis. The major signaling pathways of cell proliferation activated by ASM mitogens are those dependent on extracellular signal-regulated kinase and phosphoinositide 3'-kinase. The key signaling mechanisms of cell migration have been identified as the p38 mitogen-activated protein kinase and the p21-activated kinase 1 pathways. ASM cells contain ${\beta}2$-adrenergic receptors and glucocorticoid receptors. They may represent a key target for ${\beta}2$-adrenergic receptor agonist/corticosteroid interactions which have antiproliferative activity against a broad spectrum of mitogens.

• CELLMED
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• v.13 no.6
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• pp.7.1-7.6
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• 2023

Raphanus sativus L. has been reported to have anti-inflammatory and anti-tumor activity. However, the anti-inflammatory effect and mechanism of action of the Raphanus sativus L. seeds (RSS) with or without oil are still unknown. This study was undertaken to investigate the in-vitro anti-inflammatory effect with or without oil in the RSS on RAW 264.7 cells stimulated by lipopolysaccharide (LPS). Results showed the suppressed LPS-induced secretion of pro-inflammatory mediators such as nitric oxide (NO), inflammatory cytokine (IL-6, TNF-α). Additionally, a decrease in protein expression of iNOS was observed, but nuclear translocation of NF-κB p65 was not inhibited. To elucidate the underlying mechanism of the anti-inflammatory effect of RSS, the involvement of mitogen-activated protein kinase (MAPK) signaling pathways was examined. We also found that RSS blocked LPS-induced phosphorylation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK) signaling but did not affect the phosphorylation of p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2. These results suggest that RSS may have potential as an anti-inflammatory agent through the inhibition of LPS-induced inflammatory cytokine production via regulation of the JNK pathway.

• The Korea Journal of Herbology
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• v.22 no.2
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• pp.147-153
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• 2007

Objectives : Sophora flavescens (SF) is widely used in traditional herbal medicine in Korea and is well recognized for its anti-inflammatory effect. However, its effect on Tumornecrosis factor alpha (Tnf) production in BV2 microglial cell is not yet known. Methods : We investigated the effect of SF on the production and expression of Tnf, a well known inflammatory mediator, in lipopolysaccaride (LPS)-activated BV2 microglial cells. Results : The LPS-induced Tnf production was markedly reduced by treatment with SF (50 ${\mu}g/ml$). In reverse transcription polymerase chain reaction (RT-PCR) analysis, SF suppressed the LPS activated expression of Tnf mRNA. In addition, Western blot analysis confirmed that SF suppressed the expression of Tnf. Sophora flavescens also inhibited the LPS-induced phosphylation of extracellular signal-regulated kinases (ERK), which mediate the Tnfproduction signaling pathway whereas LPS-induced phosphylation of p38 mitogen activated protein kinase (p38 MAPK), and c-Jun NH2-terminal kinases (JNK) was not inhibited by SF, which implies that SF suppresses LPS-induced Tnf production via the ERK mediated pathway. Conclusion : Taken together, these findings indicated that SF inhibits LPS-induce Tnf production, and that this inhibitory effect is mediated via the ERK pathway.

• Tuberculosis and Respiratory Diseases
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• v.72 no.3
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• pp.275-283
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• 2012

Background: Healthy individuals who develop nontuberculous mycobacteria (NTM) lung disease are likely to have specific susceptibility factors which can lead to a NTM infection. The aim of the present study was to investigate the mechanism underlying innate immune responses, including the role of mitogen-activated protein kinase (MAPK), in Mycobacterium abscessus lung disease. Methods: Extracellular signal-regulated kinase (ERK1/2) and p38 MAPK expression in monocytes from peripheral blood mononuclear cells were measured by Western blot analysis after stimulation by Mycobacterium avium in five patients with M. abscessus lung disease and seven healthy controls. A M. avium-induced cytokine assay was performed after inhibition of ERK1/2 and p38 MAPK pathways. Results: Mycobacterium avium induced p38 and ERK1/2 expression in monocytes from healthy controls and subsequently upregulated tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and IL-10 production. In monocytes from patients with M. abscessus lung disease, however, induction of p38 and ERK1/2 expression, and the production of TNF-${\alpha}$, IL-6, and IL-10 were significantly lower. Conclusion: Decreased activity of MAPK and cytokine secretion in monocytes from patients with M. abscessus lung disease may provide an explanation regarding host susceptibility to these uncommon infections.