scholarly journals Chrysin Inhibits TNFα-Induced TSLP Expression through Downregulation of EGR1 Expression in Keratinocytes

2021 ◽  
Vol 22 (9) ◽  
pp. 4350
Author(s):  
Hyunjin Yeo ◽  
Younghan Lee ◽  
Sungshin Ahn ◽  
Euitaek Jung ◽  
Yoongho Lim ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Skin Lesions ◽  
Therapeutic Agents ◽  
Mitogen Activated Protein Kinase ◽  
Necrosis Factor Alpha ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Signaling Axis ◽  
Factor Alpha ◽  
Necrosis Factor

Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that acts as a critical mediator in the pathogenesis of atopic dermatitis (AD). Various therapeutic agents that prevent TSLP function can efficiently relieve the clinical symptoms of AD. However, the downregulation of TSLP expression by therapeutic agents remains poorly understood. In this study, we investigated the mode of action of chrysin in TSLP suppression in an AD-like inflammatory environment. We observed that the transcription factor early growth response (EGR1) contributed to the tumor necrosis factor alpha (TNFα)-induced transcription of TSLP. Chrysin attenuated TNFα-induced TSLP expression by downregulating EGR1 expression in HaCaT keratinocytes. We also showed that the oral administration of chrysin improved AD-like skin lesions in the ear and neck of BALB/c mice challenged with 2,4-dinitrochlorobenzene. We also showed that chrysin suppressed the expression of EGR1 and TSLP by inhibiting the extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2 mitogen-activated protein kinase pathways. Collectively, the findings of this study suggest that chrysin improves AD-like skin lesions, at least in part, through the downregulation of the ERK1/2 or JNK1/2-EGR1-TSLP signaling axis in keratinocytes.

scholarly journals Bacterial Lipopolysaccharide and Tumor Necrosis Factor Alpha Synergistically Increase Expression of Human Endothelial Adhesion Molecules through Activation of NF-κB and p38 Mitogen-Activated Protein Kinase Signaling Pathways

2001 ◽  
Vol 69 (3) ◽  
pp. 1273-1279 ◽  
Author(s):  
Hubertus P. A. Jersmann ◽  
Charles S. T. Hii ◽  
Judith V. Ferrante ◽  
Antonio Ferrante
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase ◽  
Adhesion Molecules ◽  
Cardiovascular Events ◽  
Tumor Necrosis ◽  
Mitogen Activated Protein Kinase ◽  
Necrosis Factor Alpha ◽  
Mitogen Activated Protein ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT One of the recognized associations of bacterial infection with cardiovascular events is the activation of endothelium and upregulation of adhesion molecules. The two major proinflammatory mediators implicated in the causation of cardiovascular events, bacterial lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF), were found to cooperate to enhance the adhesive properties of endothelial cells. These caused synergistic upregulation of intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 in human umbilical vein endothelial cells as determined by flow cytometry analysis and enzyme-linked immunosorbent assay. This synergism was not due to TNF causing an upregulation of CD14 expression. Treatment with both LPS and TNF resulted in a marked increase in the translocation of NF-κB into the nucleus. The activity of p38 mitogen-activated protein kinase was also synergistically enhanced, while the activity of c-jun N-terminal kinase was increased in an additive manner. The results demonstrate that LPS and TNF act synergistically to upregulate the expression of endothelial cell adhesion molecules, possibly by amplification of signaling pathways upstream of transcription. These findings have implications for the understanding of the acceleration of atherosclerotic events seen in low-grade infections with gram-negative organisms.

scholarly journals Nfa34810 Facilitates Nocardia farcinica Invasion of Host Cells and Stimulates Tumor Necrosis Factor Alpha Secretion through Activation of the NF-κB and Mitogen-Activated Protein Kinase Pathways via Toll-Like Receptor 4

2020 ◽  
Vol 88 (4) ◽  
Author(s):  
Xingzhao Ji ◽  
Xiujuan Zhang ◽  
Heqiao Li ◽  
Lina Sun ◽  
Xuexin Hou ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Host Cells ◽  
Mitogen Activated Protein Kinase ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT The mechanism underlying the pathogenesis of Nocardia is not fully known. The Nfa34810 protein of Nocardia farcinica has been predicted to be a virulence factor. However, relatively little is known regarding the interaction of Nfa34810 with host cells, specifically invasion and innate immune activation. In this study, we aimed to determine the role of recombinant Nfa34810 during infection. We demonstrated that Nfa34810 is an immunodominant protein located in the cell wall. Nfa34810 protein was able to facilitate the uptake and internalization of latex beads coated with Nfa34810 protein into HeLa cells. Furthermore, the deletion of the nfa34810 gene in N. farcinica attenuated the ability of the bacteria to infect both HeLa and A549 cells. Moreover, stimulation with Nfa34810 triggered macrophages to produce tumor necrosis factor alpha (TNF-α), and it also activated mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling pathways by inducing the phosphorylation of ERK1/2, p38, JNK, p65, and AKT in macrophages. Specific inhibitors of ERK1/2, JNK, and NF-κB significantly reduced the expression of TNF-α, which demonstrated that Nfa34810-mediated TNF-α production was dependent upon the activation of these kinases. We further found that neutralizing antibodies against Toll-like receptor 4 (TLR4) significantly inhibited TNF-α secretion. Taken together, our results indicated that Nfa34810 is a virulence factor of N. farcinica and plays an important role during infection. Nfa34810-induced production of TNF-α in macrophages also involves ERK, JNK, and NF-κB via the TLR4 pathway.

scholarly journals p38 Mitogen-Activated Protein Kinase-Dependent Hyperinduction of Tumor Necrosis Factor Alpha Expression in Response to Avian Influenza Virus H5N1

2005 ◽  
Vol 79 (16) ◽  
pp. 10147-10154 ◽  
Author(s):  
Davy C. W. Lee ◽  
Chung-Yan Cheung ◽  
Anna H. Y. Law ◽  
Chris K. P. Mok ◽  
Malik Peiris ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Influenza A ◽  
Tumor Necrosis ◽  
Mitogen Activated Protein Kinase ◽  
Necrosis Factor Alpha ◽  
Virus H5n1 ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Avian influenza A virus subtype H5N1 can infect humans to cause a severe viral pneumonia with mortality rates of more than 30%. The biological basis for this unusual disease severity is not fully understood. We previously demonstrated that in contrast to human influenza A virus subtypes including H1N1 or H3N2, the H5N1 virus associated with the “bird flu” outbreak in Hong Kong in 1997 (H5N1/97) hyperinduces proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α), in primary human macrophages in vitro. To delineate the molecular mechanisms involved, we analyzed the role of transcription factor NF-κB and cellular kinases in TNF-α dysregulation. H5N1 and H1N1 viruses did not differ in the activation of NF-κB or degradation of IκB-α in human macrophages. However, we demonstrated that unlike H1N1 virus, H5N1/97 strongly activates mitogen-activated protein kinase (MAPK), including p38 MAPK and extracellular signal-regulated kinases 1 and 2. Specific inhibitors of p38 MAPK significantly reduced the H5N1/97-induced TNF-α expression in macrophages. Taken together, our findings suggest that H5N1/97-mediated hyperinduction of cytokines involves the p38 MAPK signaling pathway. These results may provide insights into the pathogenesis of H5N1 disease and rationales for the development of novel therapeutic strategies.

scholarly journals Rough Lipopolysaccharide from Brucella abortus and Escherichia coli Differentially Activates the Same Mitogen-Activated Protein Kinase Signaling Pathways for Tumor Necrosis Factor Alpha in RAW 264.7 Macrophage-Like Cells

2002 ◽  
Vol 70 (12) ◽  
pp. 7165-7168 ◽  
Author(s):  
Bruce W. Jarvis ◽  
Tajie H. Harris ◽  
Nilofer Qureshi ◽  
Gary A. Splitter
Keyword(s):  
Escherichia Coli ◽  
Brucella Abortus ◽  
Tumor Necrosis ◽  
Mitogen Activated Protein Kinase ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Factor Alpha ◽  
Protein Kinase Signaling ◽  
Necrosis Factor

ABSTRACT The intracellular, gram-negative pathogen Brucella abortus establishes chronic infections in host macrophages while downregulating cytokines such as tumor necrosis factor alpha (TNF-α). When producing TNF-α, Brucella abortus rough lipopolysaccharide (LPS) activates the same mitogen-activated protein kinase signaling pathways (ERK and JNK) as Escherichia coli LPS, but Brucella LPS is a much less potent agonist.

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