scholarly journals Mojabanchromanol Isolated from Sargassum horneri Attenuates Particulate Matter Induced Inflammatory Responses via Suppressing TLR2/4/7-MAPK Signaling in MLE-12 Cells

Marine Drugs ◽  
2020 ◽  
Vol 18 (7) ◽  
pp. 355
Author(s):  
Kalahe Hewage Iresha Nadeeka Madushani Herath ◽  
Hyo Jin Kim ◽  
Jae-Hyuk Jang ◽  
Hyun-Soo Kim ◽  
Hyun Jung Kim ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Inflammatory Responses ◽  
Alveolar Epithelial Cell ◽  
Underlying Mechanism ◽  
Mapk Signaling ◽  
Sargassum Horneri ◽  
Mitogen Activated Protein Kinase ◽  
Epithelial Cell Line ◽  
Alveolar Epithelial ◽  
Mitogen Activated Protein

Chromanols from marine algae are studied for drug development due to its prominent bioactive properties, and mojabanchromanol (MC), a chromanol isolated from a brown algae Sargassum horneri, is found to possess anti-oxidant potential. In this study, we hypothesized MC may attenuate particulate matter (PM)-induced and reactive oxygen species (ROS)-mediated inflammatory responses in airways and tried to identify its potential and underlying mechanism against PM (majority <2.5 µm in diameter)-induced inflammatory responses in a lung type II alveolar epithelial cell line, MLE-12. MC attenuated PM-induced malondialdehyde (MDA), a lipid peroxidation end product, and 8-hydroxydeoxyguanosine (8-OHdG), the most representative DNA oxidative damage product, further validating MC’s potential in attenuating PM-induced oxidative stress. MC also suppressed PM-triggered TLR2/4/7 activation in MLE-12 cells. Moreover, MC reduced ROS-mediated phosphorylation of mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 1/2 (Erk1/2) and c-Jun NH (2)-terminal kinase (JNK) that were also activated in PM exposed cells. MC further inhibited the secretion of pro-inflammatory cytokines (IL-6, IL-1β and IL-33) in MLE-12 cells exposed to PM. These results provide a clear evidence for MC’s potential in attenuating PM-triggered inflammatory responses in MLE-12 cells via repressing TLR2/4/7 and MAPK signaling. Therefore, MC can be developed as a therapeutic agent against PM induced airway inflammatory responses.

scholarly journals Effect of Urban Particulate Matter on Vocal Fold Fibrosis through the MAPK/NF-κB Signaling Pathway

2020 ◽  
Vol 21 (18) ◽  
pp. 6643
Author(s):  
Ho-Ryun Won ◽  
Seung-Nam Jung ◽  
Min-Kyung Yeo ◽  
Shinae Yi ◽  
Lihua Liu ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Signaling Pathways ◽  
Vocal Fold ◽  
Animal Experiments ◽  
Vocal Folds ◽  
Underlying Mechanism ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Histological Evaluation ◽  
Mitogen Activated Protein

Particulate matter (PM) is an environmental exposure factor that adversely affects human health. PM is a risk factor for various diseases. However, the mechanism by which PM affects the vocal folds (VF) has not yet been evaluated. Thus, we investigated the cytotoxic effects of PM on human vocal fold fibroblasts (hVFF) and the underlying signaling pathways. hVFF were isolated from human VF. The effect of PM on hVFF, and the underlying mechanism, were analyzed using Western blot, quantitative real-time polymerase chain reaction, and flow cytometry. In addition, a histological evaluation was performed in animal experiments. Cell proliferation decreased after the PM treatment. PM increased the expression of interleukin (IL)-6 and IL-1β. The generation of reactive oxygen species (ROS) in PM-treated hVFF and subsequent activation of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways were confirmed. Furthermore, PM increased the expression of fibrosis-related markers and induced the accumulation of collagen in the extracellular matrix. As a result, PM exposure significantly enhances the inflammatory response on VF through the ROS-mediated activation of the MAPK and NF-κB signaling pathways. In addition, PM promotes differentiation into myofibroblasts and induces fibrosis. These results suggest that PM triggers an inflammatory reaction through ROS production and causes VF fibrosis.

scholarly journals (−)-Loliolide Isolated from Sargassum horneri Abate UVB-Induced Oxidative Damage in Human Dermal Fibroblasts and Subside ECM Degradation

Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 435
Author(s):  
Ilekuttige Priyan Shanura Fernando ◽  
Soo-Jin Heo ◽  
Mawalle Kankanamge Hasitha Madhawa Dias ◽  
Dissanayaka Mudiyanselage Dinesh Madusanka ◽  
Eui-Jeong Han ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Sargassum Horneri ◽  
Mitogen Activated Protein Kinase ◽  
Ros Generation ◽  
Protective Effects ◽  
Human Dermal Fibroblasts ◽  
Mitogen Activated Protein ◽  
Uvb Exposure

Ultraviolet (UV) B exposure is a prominent cause of skin aging and a contemporary subject of interest. The effects are progressing through the generation of reactive oxygen species (ROS) that alter cell signaling pathways related to inflammatory responses. The present study evaluates the protective effects of (7aR)-6-hydroxy-4,4,7a-trimethyl-6,7-dihydro-5H-1-benzofuran-2-one (HTT) isolated from the edible brown algae Sargassum horneri against UVB protective effects in human dermal fibroblasts (HDFs). HTT treatment dose-dependently suppressed intracellular ROS generation in HDFs with an IC50 of 62.43 ± 3.22 µM. HTT abated UVB-induced mitochondrial hyperpolarization and apoptotic body formation. Furthermore, UVB-induced activation of key nuclear factor (NF)-κB and mitogen-activated protein kinase signaling proteins were suppressed in HTT treated cells while downregulating pro-inflammatory cytokines (interleukin-1β, 6, 8, 33 and tumor necrosis factor-α). Moreover, HTT treatment downregulated matrix metalloproteinase1, 2, 3, 8, 9 and 13 that was further confirmed by the inhibition of collagenase and elastase activity. The evidence implies that HTT delivers protective effects against premature skin aging caused by UVB exposure via suppressing inflammatory responses and degradation of extracellular matrix (ECM) components. Extensive research in this regard will raise perspectives for using HTT as an ingredient in UV protective ointments.

scholarly journals Paeonol Ameliorates Ovalbumin-Induced Asthma through the Inhibition of TLR4/NF-κB and MAPK Signaling

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Yongjun Tang ◽  
Weihua Huang ◽  
Qianqian Song ◽  
Xiangrong Zheng ◽  
Ruohui He ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Inflammatory Cells ◽  
Underlying Mechanism ◽  
Lavage Fluid ◽  
Mapk Signaling ◽  
Chronic Inflammatory Disease ◽  
Mitogen Activated Protein Kinase ◽  
Asthma Model ◽  
Mitogen Activated Protein ◽  
Complex Signaling

Asthma is a chronic inflammatory disease of the airways, with complex signaling pathways involved in its pathogenesis. It was reported that paeonol attenuated airway inflammation of ovalbumin (OVA)-induced mice. Therefore, it is of importance to further investigate the underlying mechanism. BALB/c mice were challenged with OVA for the asthma model, which was validated by the changed levels of IL-4, IFN-γ, and IgE. The elevation of IL-4 and the decreasing of IFN-γ were significantly in middle (p<0.05) or high (p<0.01) paeonol dose groups compared with OVA group. MIP-1β in bronchoalveolar lavage fluid (BALF) also decreased significantly in middle and high paeonol group compared with OVA group (p<0.01), which is similar to the change of its mRNA in lung tissues. Moreover, the inflammatory cells infiltration and collagen deposition were attenuated by paeonol and montelukast sodium via histology examination. At last the immune blot of the protein extracted from lung tissues demonstrated that paeonol decreased the expression of TLR4 and the nuclear translocation of NF-κB, as well as the phosphorylation levels of P38 and ERK in asthma model. In conclusion, paeonol ameliorated OVA-induced asthma through the TLR4/NF-κB and mitogen-activated protein kinase (MAPK) signaling.

Octanal-induced inflammatory responses in cells relevant for lung toxicity

2013 ◽  
Vol 33 (7) ◽  
pp. 710-721 ◽  
Author(s):  
M-K Song ◽  
H-S Lee ◽  
H-S Choi ◽  
C-Y Shin ◽  
Y-J Kim ◽  
...  
Keyword(s):  
Pulmonary Toxicity ◽  
Inflammatory Responses ◽  
Alveolar Epithelial Cell ◽  
Lung Damage ◽  
Epithelial Cell Line ◽  
Oligonucleotide Arrays ◽  
Alveolar Epithelial ◽  
Cytokines And Chemokines ◽  
Human Alveolar Epithelial Cell ◽  
Indoor Air Pollutants

Inhalation is an important route of aldehyde exposure, and lung is one of the main targets of aldehyde toxicity. Octanal is distributed ubiquitously in the environment and is a component of indoor air pollutants. We investigated whether octanal exposure enhances the inflammatory response in the human respiratory system by increasing the expression and release of cytokines and chemokines. The effect of octanal in transcriptomic modulation was assessed in the human alveolar epithelial cell line A549 using oligonucleotide arrays. We identified a set of genes differentially expressed upon octanal exposure that may be useful for monitoring octanal pulmonary toxicity. These genes were classified according to the Gene Ontology functional category and Kyoto Encyclopedia of Genes and Genomes analysis to explore the biological processes related to octanal-induced pulmonary toxicity. The results show that octanal affects the expression of several chemokines and inflammatory cytokines and increases the levels of interleukin 6 (IL-6) and IL-8 released. In conclusion, octanal exposure modulates the expression of cytokines and chemokines important in the development of lung injury and disease. This suggests that inflammation contributes to octanal-induced lung damage and that the inflammatory genes expressed should be studied in detail, thereby laying the groundwork for future biomonitoring studies.

scholarly journals Negative Cellular Effects of Urban Particulate Matter on Human Keratinocytes Are Mediated by P38 MAPK and NF-κB-dependent Expression of TRPV 1

2018 ◽  
Vol 19 (9) ◽  
pp. 2660 ◽  
Author(s):  
Kitae Kwon ◽  
See-Hyoung Park ◽  
Byung Han ◽  
Sae Oh ◽  
Seung Lee ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Transient Receptor Potential ◽  
Inflammatory Responses ◽  
Receptor Potential ◽  
Human Keratinocytes ◽  
Underlying Mechanism ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Reporter ◽  
Transient Receptor Potential Vanilloid ◽  
Urban Particulate Matter

Urban particulate matter (UPM) exerts negative effects on various human organs. Transient receptor potential vanilloid 1 (TRPV1) is a polymodal sensory transducer that can be activated by multiple noxious stimuli. This study aimed to explore the effects of the UPM 1648a on the expression of TRPV1, and its regulatory mechanisms in HaCaT cells. UPM enhanced TRPV 1 promoter-luciferase reporter activity. UPM also increased expression of the TRPV 1 gene as evidenced by increased mRNA and protein levels of TRPV 1. In addition, elucidation of the underlying mechanism behind the UPM-mediated effects on TRPV 1 expression revealed that UPM can upregulate expression of the TRPV1 gene by activating activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). The UPM treatment also altered Ca2+ influx and cell proliferation, as well as production of interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). In addition, these UPM-induced effects were attenuated by SB203580 and ammonium pyrrolidinedithiocarbamate (PDTC). However, SP600125 and PD98059 did not alter the UPM-induced effects. Taken together, these findings indicate that UPM upregulates expression of the TRPV 1 gene, which is mediated by the p38 mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways and suggest that UPM is a potential irritant that can induce skin processes such as aging and inflammatory responses.

scholarly journals Hp-s1 Ganglioside Suppresses Proinflammatory Responses by Inhibiting MyD88-Dependent NF-κB and JNK/p38 MAPK Pathways in Lipopolysaccharide-Stimulated Microglial Cells

Marine Drugs ◽  
2020 ◽  
Vol 18 (10) ◽  
pp. 496
Author(s):  
Jui-Hu Shih ◽  
Yow-Fu Tsai ◽  
I-Hsun Li ◽  
Ming-Hua Chen ◽  
Yuahn-Sieh Huang
Keyword(s):  
P38 Mapk ◽  
Underlying Mechanism ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Microglial Cells ◽  
Cell Counting ◽  
Mitogen Activated Protein ◽  
Proinflammatory Responses ◽  
A Cell ◽  
Myeloid Differentiation Factor

Hp-s1 ganglioside is isolated from the sperm of sea urchin (Hemicentrotus pulcherrimus). In addition to neuritogenic activity, the biological function of Hp-s1 in neuroinflammation is unknown. In this study, we investigated the anti-neuroinflammatory effect of Hp-s1 on lipopolysaccharide (LPS)-stimulated microglial cells. MG6 microglial cells were stimulated with LPS in the presence or absence of different Hp-s1 concentrations. The anti-inflammatory effect and underlying mechanism of Hp-s1 in LPS-activated microglia cells were assessed through a Cell Counting kit-8 assay, Western blot analysis, and immunofluorescence. We found that Hp-s1 suppressed not only the expression of inducible nitric oxide synthase and cyclooxygenase-2 but also the expression of proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6. Hp-s1 inhibited the LPS-induced NF-κB signaling pathway by attenuating the phosphorylation and translocation of NF-κB p65 and by disrupting the degradation and phosphorylation of inhibitor κB-α (IκBα). Moreover, Hp-s1 inhibited the LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Hp-s1 also reduced the expression of myeloid differentiation factor 88 (MyD88) and TNF receptor-associated factors 6 (TRAF6), which are prerequisites for NF-κB and MAPKs activation. These findings indicated that Hp-s1 alleviated LPS-induced proinflammatory responses in microglial cells by downregulating MyD88-mediated NF-κB and JNK/p38 MAPK signaling pathways, suggesting further evaluation as a new anti-neuroinflammatory drug.

scholarly journals MicroRNA miR-126-5p Enhances the Inflammatory Responses of Monocytes to Lipopolysaccharide Stimulation by Suppressing Cylindromatosis in Chronic HIV-1 Infection

2017 ◽  
Vol 91 (10) ◽  
Author(s):  
Jun Huang ◽  
Lingyan Zhu ◽  
Chao Qiu ◽  
Xuan Xu ◽  
Linxia Zhang ◽  
...  
Keyword(s):  
Immune Activation ◽  
Inflammatory Responses ◽  
Intervention Strategy ◽  
Underlying Mechanism ◽  
Mitogen Activated Protein Kinase ◽  
Immune Intervention ◽  
Inhibitory Protein ◽  
Causative Factors ◽  
Mitogen Activated Protein ◽  
Hiv 1

ABSTRACT Persistent immune activation during chronic human immunodeficiency virus type 1 (HIV-1) infection facilitates immune dysfunction and thereby fuels disease progression. The translocation of bacterial derivatives into blood and the hyperinflammatory responsiveness of monocytes have been considered important causative factors for persistent immune activation. Whether microRNAs (miRNAs) are involved in regulating monocyte-mediated inflammatory responses during chronic HIV-1 infection remains elusive. In this study, we show that miR-126-5p functions as a positive regulator of monocyte-mediated inflammatory responses. Significantly increased miRNA miR-126-5p and decreased cylindromatosis (CYLD) were observed in primary monocytes from chronic HIV-1 patients. Inhibition of miR-126-5p in monocytes from chronic HIV-1 patients attenuated the responsiveness of these cells to lipopolysaccharide (LPS) stimulation. Gain-of-function assays confirmed that miR-126-5p could downregulate CYLD, which in turn caused an upregulation of phosphorylation of JNK protein (pJNK) and enhanced inflammatory responses of monocytes to LPS stimulation. Overall, miR-126-5p upregulates the responsiveness of monocytes to LPS stimulation in chronic HIV-1 infection, and the suppression of miR-126-5p and the promotion of CYLD expression in primary monocytes may represent a practical immune intervention strategy to contain persistent inflammation in chronic HIV-1 infection. IMPORTANCE Monocyte-mediated hyperinflammatory responses during chronic HIV-1 infection are important causative factors driving AIDS progression; however, the underlying mechanism has not been fully addressed. We demonstrated that miR-126-5p, one of the most upregulated miRNAs during chronic HIV-1 infection, could enhance the inflammatory responses of monocytes to LPS by suppressing the inhibitory protein CYLD and thereby unleashing the expression of pJNK in the LPS/Toll-like receptor 4/mitogen-activated protein kinase pathway. This observation reveals a new mechanism for HIV-1 pathogenesis, which could be targeted by immune intervention.

scholarly journals Functional Roles of p38 Mitogen-Activated Protein Kinase in Macrophage-Mediated Inflammatory Responses

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Yanyan Yang ◽  
Seung Cheol Kim ◽  
Tao Yu ◽  
Young-Su Yi ◽  
Man Hee Rhee ◽  
...  
Keyword(s):  
Protein Kinases ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Functional Roles ◽  
Cellular Processes ◽  
Cell Responses ◽  
Mitogen Activated Protein ◽  
Necrosis Factor

Inflammation is a natural host defensive process that is largely regulated by macrophages during the innate immune response. Mitogen-activated protein kinases (MAPKs) are proline-directed serine and threonine protein kinases that regulate many physiological and pathophysiological cell responses. p38 MAPKs are key MAPKs involved in the production of inflammatory mediators, including tumor necrosis factor-α(TNF-α) and cyclooxygenase-2 (COX-2). p38 MAPK signaling plays an essential role in regulating cellular processes, especially inflammation. In this paper, we summarize the characteristics of p38 signaling in macrophage-mediated inflammation. In addition, we discuss the potential of using inhibitors targeting p38 expression in macrophages to treat inflammatory diseases.

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