Electroacupuncture ameliorates cardiopulmonary bypass induced apoptosis in lung via ROS/Nrf2/NLRP3 inflammasome pathway

Dhar, Rana; Zhang, Lejun; Li, Yajun; Rana, Mohammad Nasiruddin; Hu, Zhengqiang; Li, Zigang; Cui, Hujun; Tang, Huifang

doi:10.1016/j.lfs.2019.116962

Cited by 17 publications

(13 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, EA reduces cell apoptosis, secretion of inflammatory cytokines TNF-α, IL-1β, and IL-18 in lung tissue and plasma, and alleviates pulmonary fibrosis and interstitial edema. [38][39][40] In addition to regulating NF-κB activation, TLR also promotes histone acetylation in macrophage nucleus, thereby participating in the functional activation or inhibition of the nasal mucosal and respiratory epithelial, immune cells, respectively, while regulating the pathological process via modulation of chromatin remodeling and inflammation. 41 Emerging evidence suggests that reduced histone deacetylase inhibitor 2 (HDAC2) activity partially increases the inflammatory response in the respiratory tract of COPD patients, and MA at BL13, Shenshu (BL23), and Dingchuan increases HDAC2 mRNA and protein expression in COPD rats induced by smoking.…”

Section: Monocytes/macrophagesmentioning

confidence: 99%

The Anti-Inflammatory Actions and Mechanisms of Acupuncture from Acupoint to Target Organs via Neuro-Immune Regulation

Li¹,

Guo²,

Gong³

et al. 2021

JIR

View full text Add to dashboard Cite

Inflammation plays a significant role in the occurrence and development of multiple diseases. This study comprehensively reviews and presents literature from the last five years, showing that acupuncture indeed exerts strong anti-inflammatory effects in multiple biological systems, namely, the immune, digestive, respiratory, nervous, locomotory, circulatory, endocrine, and genitourinary systems. It is well known that localized acupuncture-mediated anti-inflammatory effects involve the regulation of multiple populations and functions of immune cells, including macrophages, granulocytes, mast cells, and T cells. In acupuncture stimulation, macrophages transform from the M1 to the M2 phenotype and the negative TLR4 regulator PPARγ is activated to inhibit the intracellular TLR/MyD88 and NOD signaling pathways. The downstream IκBα/NF-κB and P38 MAPK pathways are subsequently inhibited by acupuncture, followed by suppressed production of inflammasome and proinflammatory mediators. Acupuncture also modulates the balance of helper T cell populations. Furthermore, it inhibits oxidative stress by enhancing SOD activity via the Nrf2/ HO-1 pathway and eliminates the generation of oxygen free radicals, thereby preventing inflammatory cell infiltration. The anti-inflammatory effects of acupuncture on different biological systems are also specific to individual organ microenvironments. As part of its anti-inflammatory action, acupuncture deforms connective tissue and upregulates the secretion of various molecules in acupoints, further activating the NF-κB, MAPK, and ERK pathways in mast cells, fibroblasts, keratinocytes, and monocytes/macrophages. The somatic afferents present in acupuncture-activated acupoints also convey sensory signals to the spinal cord, brainstem, and hypothalamic neurons. Upon information integration in the brain, acupuncture further stimulates multiple neuro-immune pathways, including the cholinergic anti-inflammatory, vagus-adrenal medulla-dopamine, and sympathetic pathways, as well as the hypothalamus-pituitary-adrenal axis, ultimately acting immune cells via the release of crucial neurotransmitters and hormones. This review provides a scientific and reliable basis and viewpoints for the clinical application of acupuncture in various inflammatory conditions.

show abstract

Section: Monocytes/macrophagesmentioning

confidence: 99%

The Anti-Inflammatory Actions and Mechanisms of Acupuncture from Acupoint to Target Organs via Neuro-Immune Regulation

Li¹,

Guo²,

Gong³

et al. 2021

JIR

View full text Add to dashboard Cite

show abstract

“…In this context, it is interesting to consider that Nrf2 has been reported to exert a significant inhibition of the inflammasome, the supramolecular complex involved in pyroptosis [ 131 ]. Whether Nrf2 may directly inhibit caspase 8 [ 116 ] remains to be elucidated even if caspase inhibition, including caspase 8, has been widely documented following Nrf2 activation [ 132 ]. The role of Nrf2 in viral diseases and specifically in COVID-19 is discussed below.…”

Section: Nrf2 Activation As a Strategy For Covid-19 Treatmentmentioning

confidence: 99%

The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

Emanuele

Celesia

D’Anneo

et al. 2021

IJMS

View full text Add to dashboard Cite

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known transcription factor best recognised as one of the main regulators of the oxidative stress response. Beyond playing a crucial role in cell defence by transactivating cytoprotective genes encoding antioxidant and detoxifying enzymes, Nrf2 is also implicated in a wide network regulating anti-inflammatory response and metabolic reprogramming. Such a broad spectrum of actions renders the factor a key regulator of cell fate and a strategic player in the control of cell transformation and response to viral infections. The Nrf2 protective roles in normal cells account for its anti-tumour and anti-viral functions. However, Nrf2 overstimulation often occurs in tumour cells and a complex correlation of Nrf2 with cancer initiation and progression has been widely described. Therefore, if on one hand, Nrf2 has a dual role in cancer, on the other hand, the factor seems to display a univocal function in preventing inflammation and cytokine storm that occur under viral infections, specifically in coronavirus disease 19 (COVID-19). In such a variegate context, the present review aims to dissect the roles of Nrf2 in both cancer and COVID-19, two widespread diseases that represent a cause of major concern today. In particular, the review describes the molecular aspects of Nrf2 signalling in both pathological situations and the most recent findings about the advantages of Nrf2 inhibition or activation as possible strategies for cancer and COVID-19 treatment respectively.

show abstract

“…Although previous studies have also shown that EA may alter inflammasome activation for the treatment of different inflammatory diseases. [72][73][74][75] Our studies further demonstrated that EA not only attenuated NLRP3 inflammasome activation but also suppressed the inflammatory exosome release in emphysema. Without this inflammatory exosome release, NLRP3 inflammasome activation may only induce minimal inflammatory response 76 because inflammasome products may not be released out of cells to trigger inflammatory response producing local or global inflammation in the lungs of animals or patients with emphysema.…”

Section: Discussionmentioning

confidence: 64%

“…42 Moreover, there are reports that EA inhibits NLRP3 inflammasome activation through cannabinoid B2 (CB2) receptors by endocannabinoids in inflammatory pain 72 and that ROS/Nrf2 pathway mediates EA-induced amelioration of cardiopulmonary bypass-induced apoptosis and inflammation in the lung, indicating the role of redox signaling. 73 Indeed, studies from our laboratory and by others show this redox activation of NLRP3 inflammasome in many tissues and organs. 76,[78][79][80][81] In addition, NLRP3 inflammasome activation has also been shown to be linked to extracellular vesicles such as exosome release, which is associated with an increase in intracellular ceramide.…”

Section: Discussionmentioning

confidence: 78%

Release and Actions of Inflammatory Exosomes in Pulmonary Emphysema: Potential Therapeutic Target of Acupuncture

Zou¹,

Bhat²,

Yuan³

et al. 2021

JIR

View full text Add to dashboard Cite

Background: Exosomes have been reported to mediate activation of the inflammatory response by secretion of inflammasome products such as IL-1β or IL-18 and that changes in exosomes production or secretion may be a therapeutic target for treatment of a variety of different chronic diseases. The present study tested the hypothesis that exosome-mediated release of NLRP3 inflammasome products instigates the inflammatory response in the lung during emphysema, a type of chronic obstructive pulmonary disease (COPD) and that electroacupuncture (EA) may attenuate emphysema by inhibition of NLRP3 inflammasome activation and consequent inflammation. Methods: The COPD mice model was developed by injecting porcine pancreatic elastase (PPE) via puncture tracheotomy and instillation. EA (4 Hz/20 Hz, 1 to 3 mA) was applied to the bilateral BL13 and ST36 for 30 min, once every other day for 2 weeks. Micro computed tomography (micro-CT) was performed to measure lung function. Histopathological changes in the lungs were displayed by HE staining. Results: In a mouse model of porcine pancreatic elastase (PPE)-induced emphysema, the lung tissue was found to display several key features of emphysema, including alveolar septal thickening, enlarged alveoli, interstitial edema, and inflammatory cells infiltration. Lungs of mice receiving PPE exhibited substantially increased low attenuation area (LAA) in micro-CT images. The colocalization of NLRP3 vs ASC or caspase-1 detected by confocal microscopy was shown to increase in both bronchial and alveolar walls, indicating the increased formation of NLRP3 inflammasomes. IL-1β, a prototype NLRP3 inflammasome activating product, was also found to have increased in the lung during emphysema, which was colocalized with CD63 (an exosome marker), an indicative of inflammatory exosome formation. By nanoparticle tracking analysis (NTA), IL-1β-containing exosomes were shown to significantly increase in the bronchoalveolar lavage (BAL) from mice with emphysema. Therapeutically, IL-1β production in the lung during emphysema was significantly reduced by EA at the acupoint Feishu (BL13) and Zusanli (ST36), accompanied by decreased colocalization of NLRP3 vs ASC or caspase-1. Increased exosome release into BAL during emphysema was shown to be significantly attenuated in EA-treated mice compared to their controls. However, EA of non-specific BL23 together with ST36 acupoint had no effects on NLRP3 inflammasome activation, exosome release and associated lung pathology during emphysema. Conclusion: NLRP3 inflammasome activation in concert with increased release of exosomes containing IL-1β or other inflammasome products contributes to the development of lung inflammation and injury during PPE-induced emphysema and that EA of lung-specific acupoints attenuates inflammasome activation and exosome release, thereby reducing inflammatory response in the lung of mice with emphysema.

show abstract

Electroacupuncture ameliorates cardiopulmonary bypass induced apoptosis in lung via ROS/Nrf2/NLRP3 inflammasome pathway

Cited by 17 publications

References 35 publications

The Anti-Inflammatory Actions and Mechanisms of Acupuncture from Acupoint to Target Organs via Neuro-Immune Regulation

The Anti-Inflammatory Actions and Mechanisms of Acupuncture from Acupoint to Target Organs via Neuro-Immune Regulation

The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

Release and Actions of Inflammatory Exosomes in Pulmonary Emphysema: Potential Therapeutic Target of Acupuncture

Contact Info

Product

Resources

About