A prominent air pollutant, Indeno[1,2,3-cd]pyrene, enhances allergic lung inflammation via aryl hydrocarbon receptor

Wong, Tzu Hsuan; Lee, Chon‐Lin; Su, Hsiang Han; Lee, Chin Lai; Wu, Chao Chien; Wang, Chin Chou; Sheu, Chau‐Chyun; Lai, Ruay-Sheng; Leung, Sum Yee; Lin, Chi Cheng; Wei, Yiqun; Wang, Chien Jen; Lin, Yu; Chen, Hua Ling; Huang, Ming Shyan; Yen, Jeng‐Hsien; Huang, Shau Ku; Suen, Jau‐Ling

doi:10.1038/s41598-018-23542-9

Cited by 38 publications

(29 citation statements)

References 46 publications

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“…TGF‐β and IL‐10 take on potent anti‐inflammatory effects, repressing the expression of inflammatory cytokines of IL‐6 and TNF‐α . Wong et al reported that indeno [1,2,3‐cd] pyrene which was found to be a prominent PAHs associated with ambient PM2.5, and its treatment significantly altered the function of DC, including increased level of pro‐inflammatory IL‐6 and decreased generation of anti‐inflammatory IL‐10 . Another study indicated that a cigarette smoke‐induced COPD mice model exhibited an increased pro‐inflammatory immune response (increased expression of the TNF‐α and IL‐6) with a concomitantly decreased anti‐inflammatory immune response (Foxp3, IL‐10, and TGF‐β markers) compared with the control mice .…”

Section: Resultsmentioning

confidence: 99%

Effects of phenanthrene on oxidative stress and inflammation in lung and liver of female rats

Wang

Zhang

et al. 2019

Environmental Toxicology

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Phenanthrene (Phe) female rat model was established to explore the effects of Phe on oxidative stress and inflammation. The rats were randomly divided into three groups including control (C), low (L), and high (H) group. Phe was supplied to L and H groups at the dosage of 180 mg/kg and 900 mg/kg orally at first day, and with the dose 90 mg/kg and 450 mg/kg by intraperitoneal injection at the last 2 days. The C group was enriched with the same volume of corn oil. The blood, lung, and liver tissues were collected. The superoxide dismutase (SOD), malonaldehyde (MDA), and 8-hydroxy-2-deoxyguanosine (8-OHdG) were detected to evaluate oxidative stress.The protein and mRNA expressions of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and interleukin 10 (IL-10) were detected to evaluate inflammation. Further, the forkhead box transcription factor 3 (Foxp3) was analyzed to hint the injury mechanism of inflammation. The results showed SOD and MDA in lung and liver, and serum 8-OHdG elevated significantly in H groups (P < .05). Meanwhile, there were significant increases in the protein and mRNA expression of TNF-α and IL-6 in lung and liver of H groups (P < .05). In addition, the protein and mRNA expressions of TGF-β and Foxp3 were all decreased significantly in both lung and liver of H groups (P < .05). Results demonstrated that an obvious change of Phe exposure could induce oxidative stress and inflammation in female rats. This is a first pilot study to explore the association between Phe exposure and oxidative stress and inflammation using a female rat model. K E Y W O R D Sinflammatory cytokines, liver, lung, oxidative stress, phenanthrene

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Section: Resultsmentioning

confidence: 99%

Effects of phenanthrene on oxidative stress and inflammation in lung and liver of female rats

Wang

Zhang

et al. 2019

Environmental Toxicology

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“…Asthma is characterized by chronic airway inflammation, and hyperresponsiveness (AHR) accompanied by mucus hypersecretion [1]. Triggers of allergic asthma include allergens, fungus (such as Aspergillus fumigatus [2]), viruses (mainly human rhinoviruses (HRV) [3]), and pollutants (including polycyclic aromatic hydrocarbons [4]) [5]. They interact with the airway epithelial cells to initiate the inflammatory response across the airways by releasing of cytokines, particularly IL-25, IL-33, and TSLP [5].…”

Section: Introductionmentioning

confidence: 99%

Mast Cell-Mediated Orchestration of the Immune Responses in Human Allergic Asthma: Current Insights

Komi

Bjermer

2018

Clinic Rev Allerg Immunol

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Improving the lung function after experimental allergen challenge by blocking of mast cell (MC) mediators and the capability of MC mediators (including histamine, prostaglandin (PG) D2, and leukotriene (LT) C4) in induction of mucosal edema, bronchoconstriction, and mucus secretion provide evidence that MCs play a key role in pathophysiology of asthma. In asthma, the number of MCs increases in the airways and infiltration of MCs in a variety of anatomical sites including the epithelium, the submucosal glands, and the smooth muscle bundles occurs. MC localization within the ASM is accompanied with the hypertrophy and hyperplasia of the layer, and smooth muscle dysfunction that is mainly observed in forms of bronchial hyperresponsiveness, and variable airflow obstruction. Owing to the expression of a wide range of surface receptors and releasing various cytoplasmic mediators, MCs orchestrate the pathologic events of the disease. MC-released preformed mediators including chymase, tryptase, and histamine and de novo synthesized mediators such as PGD2, LTC4, and LTE4 in addition of cytokines mainly TGFβ1, TSLP, IL-33, IL-4, and IL-13 participate in pathogenesis of asthma. The release of MC mediators and MC/airway cell interactions during remodeling phase of asthma results in persistent cellular and structural changes in the airway wall mainly epithelial cell shedding, goblet cell hyperplasia, hypertrophy of ASM bundles, fibrosis in subepithelial region, abnormal deposition of extracellular matrix (ECM), increased tissue vascularity, and basement membrane thickening. We will review the current knowledge regarding the participation of MCs in each stage of asthma pathophysiology including the releasing mediators and their mechanism of action, expression of receptors by which they respond to stimuli, and finally the pharmaceutical products designed based on the strategy of blocking MC activation and mediator release.

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“…It is expressed universally in multiple cell types: mast cells, macrophages, dendritic cells, T cells, and epithelial cells. [5][6][7][8][9][10][11][12][13] Particulate matter of 2.5 mm or less in diameter (PM2.5) is very small and can enter the airways and reach the alveoli. These small PM sizes are partly eliminated by alveolar macrophages, but some of them (especially those of <1 mm in diameter [like ultrafine particles]) pass into the blood circulation.…”

mentioning

confidence: 99%

“…5,21 Also, PMassociated PAHs have been suggested to aggravate asthma in mice. 12 Nevertheless, how the intrinsic AhR in T cells responds to PM or PAHs and regulates allergic inflammation is not known.…”

mentioning

confidence: 99%

Particulate matter of 2.5 μm or less in diameter disturbs the balance of TH17/regulatory T cells by targeting glutamate oxaloacetate transaminase 1 and hypoxia-inducible factor 1α in an asthma model

Sun

Lin

et al. 2020

Journal of Allergy and Clinical Immunology

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Background: Epidemiologic evidence suggests that exposure to particulate matter of 2.5 mm or less in diameter (PM2.5) aggravates asthma. Objective: We sought to investigate the underlying mechanisms between PM2.5 exposure and asthma severity. Methods: The relationship between PM2.5 exposure and asthma severity was investigated in an asthma model with CD4 1 T cellspecific aryl hydrocarbon receptor (AhR)-null mice. Effects of PM2.5 and polycyclic aromatic hydrocarbons (PAHs) on differentiation of T H 17/regulatory T (Treg) cells were investigated by using flow cytometry and quantitative RT-PCR. Mechanisms were investigated by using mRNA sequencing, chromatin immunoprecipitation, bisulfite sequencing, and glycolysis rates. Results: PM2.5 impaired differentiation of Treg cells, promoted differentiation of T H 17 cells, and aggravated asthma in an AhRdependent manner. PM2.5 and one of its prominent PAHs, indeno[1,2,3-cd]pyrene (IP), promoted differentiation of T H 17 cells by upregulating hypoxia-inducible factor 1a expression and enhancing glycolysis through AhRs. Exposure to PM2.5 and IP enhanced glutamate oxaloacetate transaminase 1 (Got1) expression through AhRs and accumulation of 2-hydroxyglutarate, which inhibited ten-eleven translocation methylcytosine dioxygenase 2 activity, resulting in hypermethylation in the forkhead box P3 locus and impaired differentiation of Treg cells. A GOT1 inhibitor, (aminooxy)acetic acid, ameliorated asthma by shifting differentiation of T H 17 cells to Treg cells. Similar regulatory effects of exposure to PM2.5 or IP on T H 17/Treg cell imbalance were noted in human T cells, and in a case-control design PAH exposure appeared to be a potential risk factor for asthma. Conclusions: The AhR-hypoxia-inducible factor 1a and AhR-GOT1 molecular pathways mediate pulmonary responses on exposure to PM2.5 through their ability to disturb the balance of T H 17/Treg cells.

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A prominent air pollutant, Indeno[1,2,3-cd]pyrene, enhances allergic lung inflammation via aryl hydrocarbon receptor

Cited by 38 publications

References 46 publications

Effects of phenanthrene on oxidative stress and inflammation in lung and liver of female rats

Effects of phenanthrene on oxidative stress and inflammation in lung and liver of female rats

Mast Cell-Mediated Orchestration of the Immune Responses in Human Allergic Asthma: Current Insights

Particulate matter of 2.5 μm or less in diameter disturbs the balance of TH17/regulatory T cells by targeting glutamate oxaloacetate transaminase 1 and hypoxia-inducible factor 1α in an asthma model

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