Astragalus membranaceus modulates Th1/2 immune balance and activates PPARγ in a murine asthma model

2014 ◽  
Vol 92 (5) ◽  
pp. 397-405 ◽  
Author(s):  
Shih-Ming Chen ◽  
Yau-Sheng Tsai ◽  
Su-Wen Lee ◽  
Ya-Hui Liu ◽  
Shuen-Kuei Liao ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Chinese Herb ◽  
A549 Cells ◽  
Nuclear Hormone Receptor ◽  
Astragalus Membranaceus ◽  
Luciferase Reporter ◽  
Mrna Levels ◽  
Th2 Cytokines ◽  
Asthma Model ◽  
Murine Asthma Model

Astragalus membranaceus, a traditional Chinese herb, has been used to improve airway inflammation and asthma. The present study investigated whether A. membranaceus has immunotherapeutic effects on asthma, a chronic inflammatory mucosal disease that is associated with excess production of IgE, eosinophilia, T helper 2 (Th2) cytokines, and bronchial hyperresponsiveness. An ovalbumin (OVA)-induced, chronic inflammatory airway murine asthma model was used to examine the status of pulmonary inflammation after the administration of A. membranaceus. The IgE levels in serum and bronchoalveolar lavage fluid showed a tendency to decrease after the administration of A. membranaceus. The number of eosinophils decreased and infiltration of inflammatory cells and collagen deposition declined in lung sections after A. membranaceus administration. The RNA and protein levels of Th2 cytokines and the ratio of the GATA3/T-bet mRNA levels decreased after A. membranaceus treatment. Furthermore, the mRNA level of peroxisome proliferator-activated receptor γ (PPARγ), a nuclear hormone receptor, increased in the lung tissues of A. membranaceus–treated mice. Finally, an A. membranaceus water extract activated PPARγ activity in either human embryonic kidney 293 (HEK293) or A549 cells in a PPARγ-responsive element-containing luciferase reporter assay. These results indicate that A. membranaceus has an inhibitory effect on airway inflammation in a murine model of asthma through modulating the imbalanced relationship between Th1 and Th2 cytokines.

scholarly journals The protective role of Zingerone in a murine asthma model via activation of the AMPK/Nrf2/HO-1 pathway

2020 ◽  
Author(s):  
Yingjie Zhu ◽  
Jingjing Luo ◽  
You Xu ◽  
Shucheng Hua ◽  
Dan Li ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Active Compound ◽  
Protective Role ◽  
Asthma Model ◽  
Common Illnesses ◽  
Murine Asthma Model ◽  
Chronic Airway

Asthma is one of the most common illnesses associated with chronic airway inflammation; however, there are currently no effective therapies apart from glucocorticoids. Zingerone (ZIN), an active compound isolated from...

scholarly journals PPARγ inhibits airway epithelial cell inflammatory response through a MUC1-dependent mechanism

2012 ◽  
Vol 302 (7) ◽  
pp. L679-L687 ◽  
Author(s):  
Yong Sung Park ◽  
Erik P. Lillehoj ◽  
Kosuke Kato ◽  
Choon Sik Park ◽  
Kwang Chul Kim
Keyword(s):  
Epithelial Cells ◽  
Culture Media ◽  
A549 Cells ◽  
Luciferase Reporter ◽  
Muc1 Expression ◽  
Mrna Levels ◽  
Airway Epithelial ◽  
Pparγ Agonist ◽  
Tnf Α ◽  
Primary Mouse

This study was conducted to examine the relationship between the peroxisome proliferator-associated receptor-γ (PPARγ) and MUC1 mucin, two anti-inflammatory molecules expressed in the airways. Treatment of A549 lung epithelial cells or primary mouse tracheal surface epithelial (MTSE) cells with phorbol 12-myristate 13-acetate (PMA) increased the levels of tumor necrosis factor (TNF)-α in cell culture media compared with cells treated with vehicle alone. Overexpression of MUC1 in A549 cells decreased PMA-stimulated TNF-α levels, whereas deficiency of Muc1 expression in MTSE cells from Muc1 null mice increased PMA-induced TNF-α levels. Treatment of A549 or MTSE cells with the PPARγ agonist troglitazone (TGN) blocked the ability of PMA to stimulate TNF-α levels. However, the effect of TGN required the presence of MUC1/Muc1, since no differences in TNF-α levels were seen between PMA and PMA plus TGN in MUC1/Muc1-deficient cells. Similarly, whereas TGN decreased interleukin-8 (IL-8) levels in culture media of MUC1-expressing A549 cells treated with Pseudomonas aeruginosa strain K (PAK), no differences in IL-8 levels were seen between PAK and PAK plus TGN in MUC1-nonexpressing cells. EMSA confirmed the presence of a PPARγ-binding element in the MUC1 gene promoter. Finally, TGN treatment of A549 cells increased MUC1 promoter activity measured using a MUC1-luciferase reporter gene, augmented MUC1 mRNA levels by quantitative RT-PCR, and enhanced MUC1 protein expression by Western blot analysis. These combined data are consistent with the hypothesis that PPARγ stimulates MUC1/Muc1 expression, thereby blocking PMA/PAK-induced TNF-α/IL-8 production by airway epithelial cells.

RAGE mediates airway inflammation via the HDAC1 pathway in a toluene diisocyanate-induced murine asthma model

2020 ◽  
Author(s):  
Xianru Peng ◽  
Minyu Huang ◽  
Wenqu Zhao ◽  
Zihan Lan ◽  
Xiaohua Wang ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Histone Deacetylase ◽  
Toluene Diisocyanate ◽  
Epithelial Cell Line ◽  
Akt Inhibitor ◽  
Histone Deacetylase 1 ◽  
Asthma Model ◽  
Key Words Toluene ◽  
Murine Asthma Model

Abstract BackgroundExposure to toluene diisocyanate (TDI) is a significant pathogenic factor for asthma. We previously reported that receptor for advanced glycation end products (RAGE) plays a key role in TDI-induced asthma; however, the mechanism is not clear. Epigenetic alterations of histone deacetylase (HDAC) are associated with allergic asthma. However, its effect in TDI-induced asthma is not known. The purpose of this study was to determine the role of RAGE and HDAC1 in the regulation of airway inflammation using a TDI-induced asthma model.MethodsBALB/c mice were sensitized, and challenged by TDI to establish murine asthma models. FPS-ZM1 (RAGE inhibitor), JNJ-26482585 and romidepsin (HDAC inhibitor) were given intraperitoneally before each challenge. The human bronchial epithelial cell line 16HBE was stimulated by TDI-human serum albumin (TDI-HSA) in vitro. RAGE knockdown cells were constructed and evaluated, and MK2006 (AKT inhibitor) was used in in vitro experiments.ResultsIn the TDI-induced asthmatic mice, airway reactivity, the level of Th2 cytokines in lymph supernatant, IgE, airway inflammation, and goblet cell metaplasia were all significantly increased. The increases were suppressed by FPS-ZM1, JNJ-26482585, and romidepsin. The expression of HDAC1, RAGE, and p-AKT/t-AKT was also upregulated in TDI-induced asthmatic mice, and the expressions were attenuated by FPS-ZM1. Knockdown of RAGE attenuated the upregulation of HDAC1 and phospho-AKT (p-AKT) in 16HBE cells stimulated by TDI-HSA. Treatment with the AKT inhibitor MK2006 suppressed TDI-induced HDAC1 expression. ConclusionRAGE mediates airway inflammation in a TDI-induced murine asthma model, partly via the HDAC1 pathway. Key words: Toluene diisocyanate, asthma, histone deacetylase 1, advanced glycosylation end product receptor

scholarly journals Oxygen-evoked changes in transcriptional activity of the 5′-flanking region of the human amiloride-sensitive sodium channel (αENaC) gene: role of nuclear factor κB

2002 ◽  
Vol 364 (2) ◽  
pp. 537-545 ◽  
Author(s):  
Deborah L. BAINES ◽  
Mandy JANES ◽  
David J. NEWMAN ◽  
Oliver G. BEST
Keyword(s):  
Sodium Channel ◽  
Transcriptional Activation ◽  
Transcriptional Activity ◽  
Consensus Sequence ◽  
A549 Cells ◽  
Nuclear Factor Κb ◽  
Luciferase Reporter ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Α Subunit

Expression of the α-subunit of the amiloride-sensitive sodium channel (αENaC) is regulated by a number of factors in the lung, including oxygen partial pressure (Po2). As transcriptional activation is a mechanism for raising cellular mRNA levels, we investigated the effect of physiological changes in Po2 on the activity of the redox-sensitive transcription factor nuclear factor κB (NF-κB) and transcriptional activity of 5′-flanking regions of the human αENaC gene using luciferase reporter-gene vectors transiently transfected into human adult alveolar carcinoma A549 cells. By Western blotting we confirmed the presence of NF-κB p65 but not p50 in these cells. Transiently increasing Po2 from 23 to 42mmHg for 24h evoked a significant increase in NF-κB DNA-binding activity and transactivation of a NF-κB-driven luciferase construct (pGLNF-κBpro), which was blocked by the NF-κB activation inhibitor sulphasalazine (5mM). Transcriptional activity of αENaC-luciferase constructs containing 5′-flanking sequences (including the NF-κB consensus) were increased by raising Po2 from 23 to 142mm Hg if they contained transcriptional initiation sites (TIS) for exons 1A and 1B (pGL3E2.2) or the 3′ TIS of exon 1B alone (pGL3E0.8). Sulphasalazine had no significant effect on the activity of these constructs, suggesting that the Po2-evoked rise in activity was not a direct consequence of NF-κB activation. Conversely, the relative luciferase activity of a construct that lacked the 3′ TIS, a 3′ intron and splice site but still retained the 5′ TIS and NF-κB consensus sequence was suppressed significantly by raising Po2. This effect was reversed by sulphasalazine, suggesting that activation of NF-κB mediated Po2-evoked suppression of transcription from the exon 1A TIS of αENaC.

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