Polyhexamethylene guanidine phosphate induces IL-6 and TNF-α expression through JNK-dependent pathway in human lung epithelial cells

Kim, Min-Seok; Han, Jinyoung; Kim, Sunghwan; Kim, Hyung-Young; Jeon, Doin; Lee, Kyuhong

doi:10.2131/jts.43.485

Cited by 7 publications

(5 citation statements)

References 39 publications

(52 reference statements)

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“…Adding WP9QY (TNF-α inhibitor) and N-acetylcysteine (ROS antioxidant) partially inhibited the expression of IL-8 caused by PHMB. By the way, the JNK inhibitor SP600125 could also partially inhibit the PHMG-induced expression of IL-6 and TNF-α in A549 cells (21). However, addition of the NFκB inhibitor completely inhibited the expression of IL-8, suggesting that PHMB induces inflammation through the NFκB signaling pathway (18).…”

Section: Discussionmentioning

confidence: 96%

“…Since the Korean humidifier lung injury incident, many studies have been performed to understand the mechanisms by which PHMG and its related guanidine disinfectants cause lung inflammation (10,(18)(19)(20)(21)(22) and pulmonary fibrosis (12,(22)(23)(24)(25)(26). One study showed that exposure of mouse macrophage RAW264.7 cells to PHMG decreased IκB protein expression, increased NFκB luciferase activity, and elevated the expression of inflammatory cytokines IL-1β, IL-6, and IL-8.…”

Section: Discussionmentioning

confidence: 99%

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The liver X receptor agonist T0901317 reduces the inflammation of alveolar epithelial cells induced by polyhexamethylene guanidine through inhibition of the NFκB signaling pathway

Wei¹,

Guo²,

Ding³

et al. 2021

Ann Transl Med

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Background: As a kind of disinfectant, polyhexamethylene guanidine (PHMG) can cause pulmonary inflammation. In addition to liver X receptors (LXRs) playing an important role in cholesterol and lipid metabolism, it has also been found to be involved in inflammation in recent years. This article explores the role of LXRs agonist T0901317 in the inflammation of alveolar epithelial cells induced by PHMG. Methods:The A549 human alveolar basal epithelial cell line was exposed to PHMG, T0901317, or the nuclear factor (NF)κB inhibitor BAY11-7082. The cell survival rate was used to determine the cytotoxicity of PHMG and T0901317 to A549 cells. Western blot analysis was used to determine the expression of proteins related to the LXRs and the NFκB signaling pathway. Enzyme-linked immunosorbent assay (ELISA) was conducted to examine the expression of inflammatory cytokines such as interleukin (IL)-8 and interleukin (IL)-6.Results: Incubation of A549 cells with PHMG decreased the expression of LXRs-related proteins, reduced the expression of cellular IκB, increased the expression of nuclear NFκB, and increased the levels of the inflammatory cytokineIL-8 and IL-6. However, pretreatment with the LXR agonist T0901317 partially reversed the effects of PHMG. The effects of T0901317on NFκB signaling pathway was similar to that observed with the NFκB inhibitor BAY11-7082. Conclusions:The LXRs agonist T0901317 may reduce the inflammation of alveolar epithelial cells induced by PHMG by inhibiting the NFκB signaling pathway.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

The liver X receptor agonist T0901317 reduces the inflammation of alveolar epithelial cells induced by polyhexamethylene guanidine through inhibition of the NFκB signaling pathway

Wei¹,

Guo²,

Ding³

et al. 2021

Ann Transl Med

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“…Seen in the most types of human diabetic nephropathy, the activation of the JNK pathway can worsen symptoms and inhibiting the JNK pathway is a therapeutic target for diabetic nephropathy [34]. JNKs not only have a role in the synthesis of a variety of infammatory cytokines but also the expression of proinfammatory cytokines, such as TNF-α and IL-6, is linked to the continued activation of JNK1 [35,36]. Activated by multiple pathogens and other infammatory diseases, JNK is able to phosphorylate c-Jun, triggering a series of phosphorylation cascade events and regulating critical downstream efector molecules such as TNF-α, IL-6, IL-1, ICAM-1 to exert its biological impact [37][38][39].…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology Approach to Investigate the Mechanism of Danggui‐Shaoyao‐San against Diabetic Kidney Disease

Chen

Xue

Luo

et al. 2023

Evidence-Based Complementary and Alternative Medicine

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Background. Danggui-Shaoyao-San (DSS) is a traditional Chinese medicine formula that has been widely used to treat a variety of disorders, including renal diseases. Despite being well-established in clinical practice, the mechanisms behind the therapeutic effects of DSS on diabetic nephropathy (DN) remain elusive. Methods. To explore the therapeutic mechanism, we explored the action mechanism of DSS on DN using network pharmacology strategies. All ingredients were selected from the relevant databases, and active ingredients were chosen on the basis of their oral bioavailability prediction and drug-likeness evaluation. The putative proteins of DSS were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, whereas the potential genes of DN were obtained from the GeneCards and OMIM databases. Enrichment analysis using gene ontology (GO) and the Kyoto encyclopedia of genes and genomes (KEGG) was performed to discover possible hub targets and gene-related pathways. Afterwards, the underlying molecular mechanisms of DSS against DN were validated experimentally in vivo against db/db mice. Results. We identified 91 phytochemicals using the comprehensive network pharmacology technique, 51 of which were chosen as bioactive components. There were 40 proteins and 20 pathways in the target-pathway network. The experimental validation results demonstrated that DSS may reduce the expression of TNF-α, IL-6, and ICAM-1, as well as extracellular matrix deposition, by blocking the JNK pathway activation, which protects against kidney injury. Conclusion. This study discovered the putative molecular mechanisms of action of DSS against diabetic kidney damage through a network pharmacology approach and experimental validation.

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“…One in vivo study of PGH showed that exposure through intratracheal instillation in mice can increase cytokine and fibronectin levels [ 10 ]. In vivo studies of PHMG also showed that exposure through inhalation and intratracheal instillation in rats can induce the release of pro-inflammatory cytokines and cause fibronectin mRNA expression and histopathological changes in lung tissues [ 26 , 27 ]. In vitro studies of PHMG and CMIT/MIT suggested that their exposures can induce the release of proinflammatory cytokines in macrophages and alveolar epithelial cells in mice, respectively [ 8 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

New-Onset and Exacerbation of Lung Diseases after Short-Term Exposures to Humidifier Disinfectant during Hospitalization

Lee

Han

Yoon

et al. 2022

Toxics

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(1) Background: Humidifier disinfectant (HD) is a biocidal chemical to keep the water tank inside a humidifier clean. Thousands of Koreans have experienced HD-related lung injuries. Of them, 6.9% were exposed to HD in hospitals. (2) Methods: This study investigated changes of diseases in patients (or caregivers) who experienced HD exposures during hospitalization and also investigated characteristics of hospital exposure using data from all HD-related lung injury enrollment in Korea. (3) Results: Of a total of 162 subjects, 139 subjects were hospitalized for non-lung diseases, and 23 people were hospitalized for lung diseases at the time of hospitalization. During hospital exposure, 99 (71.2%) of those hospitalized with non-lung disease experienced a new-onset of lung disease, and 15 (65.2%) of those hospitalized with lung diseases experienced exacerbation of their existing lung diseases. When we compared their exposure characteristics, those exposed in hospitals (vs. non-hospital, mostly home) were exposed for shorter periods, at closer distances, at higher HD indoor concentrations, constantly all day, and directly in the facial direction. (4) Conclusion: In conclusion, HD exposures in hospital with a high intensity even for a short term were associated with new-onset or exacerbation of lung diseases. Our findings suggest that acute exposures to HD can cause lung diseases.

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Polyhexamethylene guanidine phosphate induces IL-6 and TNF-α expression through JNK-dependent pathway in human lung epithelial cells

Cited by 7 publications

References 39 publications

The liver X receptor agonist T0901317 reduces the inflammation of alveolar epithelial cells induced by polyhexamethylene guanidine through inhibition of the NFκB signaling pathway

The liver X receptor agonist T0901317 reduces the inflammation of alveolar epithelial cells induced by polyhexamethylene guanidine through inhibition of the NFκB signaling pathway

Network Pharmacology Approach to Investigate the Mechanism of Danggui‐Shaoyao‐San against Diabetic Kidney Disease

New-Onset and Exacerbation of Lung Diseases after Short-Term Exposures to Humidifier Disinfectant during Hospitalization

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