• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.23 no.2
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• pp.57-68
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• 2010

Objective : This study was performed to evaluate the effect of Lithospermum erythrorhizon extracts on the inflammatory cytokines gene expression by the bacteria of Propionibacterium acnes (P. acnes) which elicits acne in human monocytes, THP-1 cell line. Experiment : Cytotoxicity of Lithospermum erythrorhizon extracts was analyzed by XTT assay. Real time RT-PCR was applied to analyze the cytokines gene expressions of IL-8, MCP-1 and TNF-$\alpha$. Translocation of transcription factor NF-${\kappa}B$ from cytoplasm into nucleus was observed using immunocytochemistry and confocal microscopy. Results : Lithospermum erythrorhizon extracts did not show cytotoxicity as high as in $1,000\;{\mu}g/ml$ of concentration. Transcription levels of inflammatory cytokines, IL-8, MCP-1 and TNF-$\alpha$ were increased by P. acnes in THP-1 and Lithospermum erythrorhizon extracts decreased the upregulated transcription levels. Lithospermum erythrorhizon extracts significantly inhibited the translocation of NF-${\kappa}B$ into nucleus by P. acnes. Conclusion : This study suggests that Lithospermum erythrorhizon extracts have anti-inflammatory effects on P. acnes treated THP-1 as decreasing the mRNA expressions of IL-8, MCP-1 and TNF-$\alpha$. This anti-inflammatory effect of Lithospermum erythrorhizon extracts may be useful in therapeutic treatments for acne vulgaris.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.2
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• pp.177-185
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• 2023

The excessive inflammatory response induced by myocardial infarction exacerbates heart injury and leads to the development of heart failure. Recent studies have confirmed the involvement of multiple transcription factors in the modulation of cardiovascular disease processes. However, the role of KLF9 in the inflammatory response induced by cardiovascular diseases including myocardial infarction remains unclear. Here, we found that the expression of KLF9 significantly increased during myocardial infarction. Besides, we also detected high expression of KLF9 in infiltrated macrophages after myocardial infarction. Our functional studies revealed that KLF9 deficiency prevented cardiac function and adverse cardiac remodeling. Furthermore, the downregulation of KLF9 inhibited the activation of NF-κB and MAPK signaling, leading to the suppression of inflammatory responses of macrophages triggered by myocardial infarction. Mechanistically, KLF9 was directly bound to the TLR2 promoter to enhance its expression, subsequently promoting the activation of inflammation-related signaling pathways. Our results suggested that KLF9 is a pro-inflammatory transcription factor in macrophages and targeting KLF9 may be a novel therapeutic strategy for ischemic heart disease.

• BMB Reports
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• v.36 no.1
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• pp.95-109
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• 2003

Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance. The sources of the increased oxidative stress in patients with chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) derive from the increased burden of inhaled oxidants, and from the increased amounts of reactive oxygen species (ROS) generated by several inflammatory, immune and various structural cells of the airways. Increased levels of ROS produced in the airways is reflected by increased markers of oxidative stress in the airspaces, sputum, breath, lungs and blood in patients with lung diseases. ROS, either directly or via the formation of lipid peroxidation products such as 4-hydroxy-2-nonenal may play a role in enhancing the inflammation through the activation of stress kinases (JNK, MAPK, p38) and redox sensitive transcription factors such as NF-${\kappa}B$ and AP-1. Recent evidences have indicated that oxidative stress and pro-inflammatory mediators can alter nuclear histone acetylation/deacetylation allowing access for transcription factor DNA binding leading to enhanced pro-inflammatory gene expression in various lung cells. Understanding of the mechanisms of redox signaling, NF-${\kappa}B$/AP-1 regulation, the balance between histone acetylation and deacetylation and the release and expression of pro- and anti-inflammatory mediators may lead to the development of novel therapies based on the pharmacological manipulation of antioxidants in lung inflammation and injury. Antioxidants that have effective wide spectrum activity and good bioavailability, thiols or molecules which have dual antioxidant and anti-inflammatory activity, may be potential therapeutic agents which not only protect against the direct injurious effects of oxidants, but may fundamentally alter the underlying inflammatory processes which play an important role in the pathogenesis of chronic inflammatory lung diseases.

• Toxicological Research
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• v.25 no.4
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• pp.159-173
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• 2009

Nuclear factor erythroid derived 2-related factor-2 (Nrf2) is a master transcription regulator of antioxidant and cytoprotective proteins that mediate cellular defense against oxidative and inflammatory stresses. Disruption of cellular stress response by Nrf2 deficiency causes enhanced susceptibility to infection and related inflammatory diseases as a consequence of exacerbated immune-mediated hypersensitivity and autoimmunity. The cellular defense capacity potentiated by Nrf2 activation appears to balance the population of $CD4^+$ and $CD8^+$ of lymph node cells for proper innate immune responses. Nrf2 can negatively regulate the activation of pro-inflammatory signaling molecules such as p38 MAPK, NF-${\kappa}B$, and AP-1. Nrf2 subsequently functions to inhibit the production of pro-inflammatory mediators including cytokines, chemokines, cell adhesion molecules, matrix metalloproteinases, COX-2 and iNOS. Although not clearly elucidated, the antioxidative function of genes targeted by Nrf2 may cooperatively regulate the innate immune response and also repress the expression of pro-inflammatory mediators.

• Parasites, Hosts and Diseases
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• v.62 no.1
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• pp.30-41
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• 2024

The dense granule protein of Toxoplasma gondii, inhibitor of signal transducer and activator of transcription 1 (IST) is an inhibitor of signal transducer and activator of transcription 1 (STAT1) transcriptional activity that binds to STAT1 and regulates the expression of inflammatory molecules in host cells. A sterile inflammatory liver injury in pathological acute liver failures occurs when excessive innate immune function, such as the massive release of IFN-γ and TNF-α, is activated without infection. In relation to inflammatory liver injury, we hypothesized that Toxoplasma gondii inhibitor of STAT1 transcription (TgIST) can inhibit the inflammatory response induced by activating the STAT1/IRF-1 mechanism in liver inflammation. This study used IFN-γ and TNF-α as inflammatory inducers at the cellular level of murine hepatocytes (Hepa-1c1c7) to determine whether TgIST inhibits the STAT1/IRF-1 axis. In stable cells transfected with TgIST, STAT1 expression decreased with a decrease in interferon regulatory factor (IRF)-1 levels. Furthermore, STAT1 inhibition of TgIST resulted in lower levels of NF-κB and COX2, as well as significantly lower levels of class II transactivator (CIITA), iNOS, and chemokines (CLXCL9/10/11). TgIST also significantly reduced the expression of hepatocyte proapoptotic markers (Caspase3/8/9, P53, and BAX), which are linked to sterile inflammatory liver injury. TgIST also reduced the expression of adhesion (ICAM-1 and VCAM-1) and infiltration markers of programmed death-ligand 1 (PD-L1) induced by hepatocyte and tissue damage. TgIST restored the cell apoptosis induced by IFN-γ/TNF-α stimulation. These results suggest that TgIST can inhibit STAT1-mediated inflammatory and apoptotic responses in hepatocytes stimulated with proinflammatory cytokines.

• International Journal of Molecular Medicine
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• v.43 no.6
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• pp.2516-2522
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• 2019

Particulate matter (PM), a widespread airborne contaminant, is a complex mixture of solid and liquid particles suspended in the air. Recent studies have demonstrated that PM induces oxidative stress and inflammatory reactions, and may cause certain skin diseases. Afzelin is a flavonoid isolated from Thesium chinense Turcz, which has anti-inflammatory, anticancer and antibacterial properties. Therefore, the present study aimed to investigate if afzelin affected inflammatory responses in human keratinocytes exposed to PM. HaCaT cells were treated with PM (25 ㎍/cm2) in the presence or absence of afzelin (200 µM). Here, standard reference material 1649b was used as PM. Cell viability was assessed using the water-soluble tetrazolium salt-1 assay. The generation of reactive oxygen species (ROS) was measured using the dichloro-dihydro-​fluorescein diacetate assay. Gene and protein expression were investigated using reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Levels of secreted inflammatory cytokines were measured using ELISA. The results suggested that afzelin inhibited PM-induced proinflammatory cytokine mRNA expression and protein secretion in HaCaT cells. In addition, afzelin suppressed PM-induced intracellular ROS generation, and p38 mitogen-activated protein kinase and transcription factor activator protein-1 component c-Fos and c-Jun activation. The results indicated that afzelin exerts anti-inflammatory and antioxidant effects in PM-exposed HaCaT. Afzelin may have potential for preventing PM-induced inflammatory skin diseases.

• Journal of dental hygiene science
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• v.19 no.4
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• pp.254-260
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• 2019

Background: The primary aims of periodontal disease treatment is to remove dental plaque and calculus, the main causes of tooth loss, and restore periodontal tissue destroyed by inflammation. Periodontal disease treatment should also help maintain the alveolar bone, alleviate inflammation, and promote periodontal ligament cell proliferation, which is essential for tissue regeneration. Conventional antibiotics and anti-inflammatories have adverse side effects, especially during long-term use, so there is a need for adjunct treatment agents derived from natural products. The purpose of this study was to investigate whether the herbal flavone baicalein has the osteogenic activity under inflammatory conditions, and assess the involvement of osteoblast immediate early response 3 (IER3) expression. Methods: Human osteoblastic MG-63 cells were cultured with the pro-inflammatory cytokines tumor necrosis factor α and interleukin 1β in the presence and absence of baicalein. Proliferation was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, and expression of IER3 mRNA was assessed using real-time polymerase chain reaction. The expression of IER3 protein levels and activation of associated signal transduction pathways were assessed using western blotting. Results: Baicalein increased IER3 mRNA and protein expression synergistically. In addition, baicalein reversed the suppression of cell proliferation, and the downregulation of osteogenic transcription factor runt-related transcription factor 2 and osterix induced by pro-inflammatory cytokines. Baicalein also upregulated the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK 1/2). The upregulation of IER3 by pro-inflammatory cytokines was blocked by pretreatment with inhibitors of AKT, p38, JNK, and ERK 1/2. Conclusion: Baicalein mitigates the deleterious responses of osteoblasts to pro-inflammatory cytokines. Further, IER3 enhanced the effect of baicalein via activation of AKT, p38, JNK, and ERK pathways.

• Journal of Microbiology
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• v.39 no.3
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• pp.186-194
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• 2001

Scrub typhus, caused by Orientia tsutsugamushi infection, is clinically and histopathologically characterized by local as well as systemic inflammatory reactions, indicating that orientiae induce mechanisms that amplify the inflammatory response. To reveal underlying mechanisms of chemoattraction and activation of responding leukocytes, expression of chemokine and tumor necrosis factor alpha (TNF-$\alpha$) genes in murine peritoneal macrophages after infection with the obligate intracellular bacterium Ο.tsutsugamushi was investigated. The genes that were unregulated included macrophage inflammatory proteins l$\alpha$/$\beta$(MIP-l$\alpha$/$\beta$), MIP-2, monocyte chemoattractant protein 1(MCP-1), RANTES (regulated upon activation, normal T-cell expressed and secreted), gamma-interferon-inducible protein 10(IP-10) and TNF-$\alpha$. Peak expression of these chemokines and TNF-$\alpha$ was observed between 1 and 3 h after infection. These responses returned to or approached baseline preinfection levels 6 h after challenge. Semiquantitative reverse transcription (RT)-PCR analysis revealed dramatic Increases during infection in the steady-state levels of mRNA ceding for the inhibitory subunit of NF-kB (IkB$\alpha$), whose transcription is enhanced by binding of NF-kB within the IkB$\alpha$promoter region. Thus, Ο. tsutsugamushi appears to be a stung inducer of chemokines and TNF-$\alpha$ which may significantly contribute to inflammation and tissue damage observed in scrub typhus by attracting and activating phagocytic leukocytes.

• Natural Product Sciences
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• v.21 no.3
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• pp.205-209
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• 2015

Fucoidan, a sulfated polysaccharide is found in several types of edible brown algae. It has shown numerous biological activities; however, the molecular mechanisms on the activity against atopic dermatitis have not been reported yet. We now examined the effects of fucoidan on chemokine production co-induced by TNF-α/IFN-γ, and the possible mechanisms underlying these biological effects. Our data showed that fucoidan inhibited the TNF-α/IFN-γ-induced production of thymus and activation-regulated chemokine (TARC) and macrophagederived chemokine (MDC) mRNA in human keratinocytes HaCaT cells. Also, fucoidan suppressed phosphorylation of nuclear factor kappa B (NF-κB) and activation of signal transducer and activator of transcription (STAT)1 in a dose-dependent manner. In addition, fucoidan significantly inhibited activation of extracellular-signal-regulated kinases (ERK) phosphorylation. These data indicate that fucoidan shows anti-inflammatory effects by suppressing the expression of TNF-α/IFN-γ-induced chemokines by blocking NF-κB, STAT1, and ERK1/2 activation, suggestive of as used as a therapeutic application in inflammatory skin diseases, such as atopic dermatitis.

• Journal of Life Science
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• v.24 no.7
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• pp.713-720
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• 2014

In this study, the antioxidative and anti-inflammatory activities of Ardisia arborescens ethanol extract (AAEE) were evaluated using in vitro assays and a cell culture model system. AAEE exhibited potent scavenging activity against 1,1-diphenyl-2-picryl hydrazyl (DPPH), similar to ascorbic acid, which was used as a positive control. Moreover, AAEE effectively suppressed lipopolysaccharide (LPS)- and hydrogen peroxide ($H_2O_2$)-induced reactive oxygen species (ROS) in RAW 264.7 cells. Furthermore, AAEE induced the expression of antioxidative enzymes, heme oxygenase 1 (HO-1), and thioredoxin reductase 1 (TrxR1), in addition to their upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2), in a dose-dependent manner. The upstream signaling pathways of mitogen-activated protein kinases (MAPKs) might regulate the modulation of HO-1, TrxR1, and Nrf2 expression. On the other hand, AAEE inhibited LPS-induced nitric oxide (NO) formation, without cytotoxicity. Suppression of NO formation was the result of AEEE-induced down-regulation of inducible NO synthase (iNOS). The suppression of NO and iNOS by AAEE might be modulated by their upstream transcription factor, nuclear factor (NF)-${\kappa}B$, and activator protein (AP)-1 pathways. Taken together, these results provide important new insights into the antioxidative and anti-inflammatory activities of A. arborescens. AAAEE might represent a promising material in the field of nutraceuticals.