Berberine Inhibits Pro-inflammatory Cytokine-induced IL-6 and CCL11 Production via Modulation of STAT6 Pathway in Human Bronchial Epithelial Cells

Ma, Jason; Chan, Chiu‐Po; Huang, Wen‐Chung; Kuo, Ming‐Ling

doi:10.7150/ijms.45400

Cited by 30 publications

(21 citation statements)

References 48 publications

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“…Eosinophilic inflammatory response, which is characteristic of asthma, is known to be induced by IL-4, IL-5, and IL-13 produced by CD4 + T helper type 2 (Th2) cells [ 21 ]. Furthermore, proinflammatory cytokines such as TNF-α, IL-6, and IL-1β, function as growth factors for B cells and play an important role in the differentiation of CD4 + Th2 cells [ 22 ]. These cytokines have been reported to increase the secretion of mucus by stimulating goblet cells of bronchi, resulting in AHR [ 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

Titanium Dioxide Nanoparticles Exacerbate Allergic Airway Inflammation via TXNIP Upregulation in a Mouse Model of Asthma

Lim

Lee

Kim

et al. 2021

IJMS

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Titanium dioxide nanoparticles (TiO2NPs) are widely used in industrial and medicinal fields and in various consumer products, and their increasing use has led to an increase in the number of toxicity studies; however, studies investigating the underlying toxicity mechanism have been rare. In this study, we evaluated potential toxic effects of TiO2NPs exposure on lungs as well as the development of asthma through the ovalbumin (OVA)-induced mouse model of asthma. Furthermore, we also investigated the associated toxic mechanism. TiO2NPs caused pulmonary toxicity by exacerbating the inflammatory response, indicated by an increase in the number and level of inflammatory cells and mediators, respectively. OVA-induced asthma exposed mice to TiO2NPs led to significant increases in inflammatory mediators, cytokines, and airway hyperresponsiveness compared with those in non-exposed asthmatic mice. This was also accompanied by increased inflammatory cell infiltration and mucus production in the lung tissues. Additionally, TiO2NPs decreased the expression of B-cell lymphoma 2 (Bcl2) and the expressions of thioredoxin-interacting protein (TXNIP), phospho-apoptosis signal-regulating kinase 1, Bcl2-associated X, and cleaved-caspase 3 were escalated in the lungs of asthmatic mice compared with those in non-exposed asthmatic mice. These responses were consistent with in vitro results obtained using human airway epithelial cells. TiO2NPs treated cells exhibited an increase in the mRNA and protein expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α with an elevation of TXNIP signaling compared to non-treated cells. Moreover, pathophysiological changes induced by TiO2NP treatment were significantly decreased by TXNIP knockdown in airway epithelial cells. Overall, TiO2NP exposure induced toxicological changes in the respiratory tract and exacerbated the development of asthma via activation of the TXNIP-apoptosis pathway. These results provide insights into the underlying mechanism of TiO2NP-mediated respiratory toxicity.

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Section: Discussionmentioning

confidence: 99%

Titanium Dioxide Nanoparticles Exacerbate Allergic Airway Inflammation via TXNIP Upregulation in a Mouse Model of Asthma

Lim

Lee

Kim

et al. 2021

IJMS

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“…Eosinophilic in ammatory response, which is characteristic of asthma, is known to be induced by IL-4, IL-5, and IL-13 produced by CD4 + T helper type 2 (Th2) cells [20]. In addition, proin ammatory cytokines, such as TNF-α, IL-6, and IL-1β, function as growth factors for B cells and play an important role in the differentiation of CD4 + Th2 cells [21]. These cytokines have been reported to increase the secretion of mucus by stimulating the goblet cells of bronchi, resulting in AHR [22,23].…”

Section: Discussionmentioning

confidence: 99%

Titanium dioxide nanoparticles exacerbate allergic airway inflammation via TXNIP upregulation in a mouse model of asthma

Lim

Lee

Kim

et al. 2021

Preprint

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Background Titanium dioxide nanoparticles (TiO2NPs) are widely used in the fields of industry and medicine and in various consumer products. With the increasing use of TiO2NPs, there has been an increase in the number of toxicity studies; however, studies investigating the mechanism underlying its toxicity are very rare. In this study, we evaluated the potential toxic effects of TiO2NPs exposure on the lungs as well as the development of asthma in ovalbumin (OVA)-induced mouse model of asthma. We also investigated the related toxic mechanism. Results TiO2NPs caused pulmonary toxicity by exacerbating the inflammatory response, indicated by an increase in the number of inflammatory cells and levels of inflammatory mediators. Exposure of mice with OVA-induced asthma to TiO2NPs led to significant increases in inflammatory mediators, cytokines, and airway hyperresponsiveness compared with non-exposed mice with asthma. This was also accompanied by an increase in inflammatory cell infiltration and mucus production in the lung tissues. TiO2NPs also decreased the expression of B-cell lymphoma 2 (Bcl2) and increased the expression of thioredoxin-interacting protein (TXNIP), phospho-apoptosis signal-regulating kinase 1, Bcl2-associated X, and cleaved-caspase 3 in the lungs of asthmatic mice compared with those of non-exposed asthmatic mice. These responses were consistent with in vitro results obtained using human airway epithelial cells. TiO2NPs treated cells exhibited an increase in the mRNA and protein expression of IL-1β, IL-6, and TNF-α with an elevation of TXNIP signaling compared to non-treated cells. Moreover, pathophysiological changes induced by TiO2NPs treatment were significantly decreased by TXNIP knockdown in the airway epithelial cells. Conclusion Taken together, TiO2NPs exposure induced toxicological changes in the respiratory tract and exacerbated the development of asthma via activation of the TXNIP-apoptosis pathway. These results provide insights into the mechanism underlying TiO2NPs-mediated respiratory toxicity.

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“… 10 , 11 Signal transducer and activator of transcription 6 regulates Th2 cell differentiation and mediates IL-4/IL-13-induced eotaxin (CCL11) production, resulting in eosinophilic infiltration. 12 , 13 Recently, the STAT6 signaling pathway has gained increasing attention in the field of nasal allergic diseases. It was found that phosphorylated STAT6 (p-STAT6) was overexpressed in the sinonasal tissues of an eosinophilic CRSwNP mouse model.…”

Section: Introductionmentioning

confidence: 99%

Activation of STAT6 by intranasal allergens correlated with the development of eosinophilic chronic rhinosinusitis in a mouse model

Wei

Sun

et al. 2022

Int J Immunopathol Pharmacol

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Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory disease characterized by prominent eosinophilic infiltration along with a T-helper-2 (Th2) response. It has been well documented that signal transducer and activator of transcription 6 (STAT6) is a nuclear transcription factor that mediates Th2-type immunity and is implicatory of STAT1 and STAT3 in the pathogenesis of allergic airway diseases. However, little is known about the association between STATs and ECRS. Here, we explored the relationship between STAT1, STAT3, and/or STAT6 and eosinophilic inflammation accompanied by Th2-type immunity in a mouse model of ECRS. An ovalbumin (OVA)-staphylococcal enterotoxin B (SEB)-induced ECRS murine model was first established. The mucosal histological alterations were determined using hematoxylin and eosin staining. The number of eosinophils in peripheral blood was measured using a blood cell analyzer. The cytokine (IL-4, IL-5, IL17 A and IFN-γ) expression levels in the sinonasal mucosa and total and OVA-specific IgE from serum were measured using ELISA. Then, the protein levels of STAT1, STAT3, STAT6, phosphorylated STAT1 (p-STAT1), p-STAT3, p-STAT6, T-box expressed in T-cells (T-bet), GATA binding protein 3 (GATA-3), and retinoic acid receptor-related orphan receptor γ (RORγt) in the sinonasal mucosa were examined by immunohistochemical staining or Western blotting. Local administration of OVA combined with SEB (OVA + SEB) induced multiple polyp-like lesions, accompanied by prominent eosinophilic infiltration in the sinonasal mucosa. The OVA- and OVA+SEB-treated groups showed significantly higher eosinophil counts from peripheral blood and total and OVA-specific IgE levels from serum than those in the PBS- and SEB-treated groups. The levels of p-STAT6 were markedly increased by OVA + SEB exposure, as well as GATA-3, IL-4, and IL-5, but did not affect STAT6, p-STAT1, p-STAT3, T-bet, RORγt, IFN-γ, or IL-17A. Furthermore, an eosinophil count in the sinonasal mucosa showed a positive correlation with the level of p-STAT6 in the ECRS mouse model. Signal transducer and activator of transcription 6 signaling could be activated in the OVA+SEB-induced ECRS model and might be a crucial signal transducer in the development of Th2-skewed ECRS.

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Berberine Inhibits Pro-inflammatory Cytokine-induced IL-6 and CCL11 Production via Modulation of STAT6 Pathway in Human Bronchial Epithelial Cells

Cited by 30 publications

References 48 publications

Titanium Dioxide Nanoparticles Exacerbate Allergic Airway Inflammation via TXNIP Upregulation in a Mouse Model of Asthma

Titanium Dioxide Nanoparticles Exacerbate Allergic Airway Inflammation via TXNIP Upregulation in a Mouse Model of Asthma

Titanium dioxide nanoparticles exacerbate allergic airway inflammation via TXNIP upregulation in a mouse model of asthma

Activation of STAT6 by intranasal allergens correlated with the development of eosinophilic chronic rhinosinusitis in a mouse model

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