Effect of Liuweibuqi Capsules in Pulmonary Alveolar Epithelial Cells and COPD Through JAK/STAT Pathway

Wang, Chengyang; Ding, Huanzhang; Tang, Xianfeng; Li, Zegeng; Gan, Lei

doi:10.1159/000481558

Cited by 18 publications

(23 citation statements)

References 39 publications

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“… 67 Furthermore, the JAK2/STAT3 signaling pathway has been shown to play an important regulatory role in microglial reactivity to various stimuli and mediates proinflammatory responses in microglia in response to various insults. 73 – 75 In the present study, in early-stage DNP in STZ-induced DNP rats, the increased expression of IL-6 and JAK2/STAT3 in the dorsal spinal cord could be significantly suppressed by MRS2211. Dominguez et al suggested that intrathecal injection of anti-rat IL-6 antibodies obviously prevented SNL-induced accumulation of phospho-STAT3 in dorsal spinal cord microglia.…”

Section: Discussionsupporting

confidence: 46%

Activation of spinal dorsal horn P2Y<sub>13</sub> receptors can promote the expression of IL-1β and IL-6 in rats with diabetic neuropathic pain

Zhou

Liu

et al. 2018

JPR

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ObjectiveThe dorsal horn P2Y13 receptor is involved in the development of pain behavior induced by peripheral nerve injury. It is unclear whether the expression of proinflammatory cytokines interleukin (IL)-1β and IL-6 at the spinal dorsal horn are influenced after the activation of P2Y13 receptor in rats with diabetic neuropathic pain (DNP).MethodsA rat model of type 1 DNP was induced by intraperitoneal injection of streptozotocin (STZ). We examined the expression of P2Y13 receptor, Iba-1, IL-1β, IL-6, JAK2, STAT3, pTyr1336, and pTyr1472 NR2B in rat spinal dorsal horn.ResultsCompared with normal rats, STZ-diabetic rats displayed obvious mechanical allodynia and the increased expression of P2Y13 receptor, Iba-1, IL-1β, and IL-6 in the dorsal spinal cord that was continued for 6 weeks in DNP rats. The data obtained indicated that, in DNP rats, administration of MRS2211 significantly attenuated mechanical allodynia. Compared with DNP rats, after MRS2211 treatment, expression of the P2Y13 receptor, Iba-1, IL-1β, and IL-6 were reduced 4 weeks after the STZ injection. However, MRS2211 treatment did not attenuate the expression of the P2Y13 receptor, Iba-1, IL-1β, and IL-6 at 6 weeks after the STZ injection. MRS2211 suppressed JAK2 and STAT3 expression in the early stage, but not in the later stage. Moreover, pTyr1336 NR2B was significantly decreased, whereas pTyr1472 NR2B was unaffected in the dorsal spinal cord of MRS2211-treated DNP rats.ConclusionIntrathecal MRS2211 produces an anti-nociceptive effect in early-stage DNP. A possible mechanism involved in MRS2211-induced analgesia is that blocking the P2Y13 receptor downregulates levels of IL-1β and IL-6, which subsequently inhibit the activation of the JAK2/STAT3 signaling pathway. Furthermore, blocking the activation of the P2Y13 receptor can decrease NR2B-containing NMDAR phosphorylation in dorsal spinal cord neurons, thereby attenuating central sensitization in STZ-induced DNP rats.

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Section: Discussionsupporting

confidence: 46%

Activation of spinal dorsal horn P2Y<sub>13</sub> receptors can promote the expression of IL-1β and IL-6 in rats with diabetic neuropathic pain

Zhou

Liu

et al. 2018

JPR

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“…COPD is characterized by presence of progressive and poorly reversible airflow limitation and linked to abnormal inflammatory response to harmful particles or gases in the airways and the lungs [ 2 ]. It is reported that multiple processes such as inflammation, cellular apoptosis, oxidative stress, and abnormal cellular repair are involved in the pathogenesis of COPD [ 3 ]. AECOPD is a serious event that is responsible for the progress of the disease and thus increased mortality [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Xiaoqinglong Decoction Protects the Lungs of AECOPD Mice through the AMPK/mTOR Signaling Pathway

Huang

Yang

Zhang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Background/Aim. Chronic obstructive pulmonary disease (COPD) is one of the most common health problems around the world. Xiaoqinglong decoction (XQLD) has been clinically reported to improve lung function and shorten cough and sputum in AECOPD patients, but its mechanism is still unclear. This study aims to investigate the effects of XQLD on inflammation and apoptosis of lung tissues and explore the underlying mechanisms in acute exacerbation in COPD (AECOPD) mice. Method. Male C57BL/6J mice were used to establish AECOPD model by cigarette smoke and bacterial exposure. Mice were randomly divided into normal control (NC), AECOPD, XQLD, Compound C (Com C), Com C + XQLD, and Clarithromycin (CLA) groups. After treatment, the pulmonary function was evaluated by whole-body plethysmograph. The lung histopathology was observed by HE staining. The serum levels of IL-6, TNF-α, and COX-2 were detected by ELISA assay. The apoptotic index was measured by TUNEL assay, and the protein expressions of Bax, Bcl-2, Caspase-3, GRP78, and CHOP in the lung tissues were measured by western blot assay. Results. XQLD treatment can improve pulmonary function (PF), ameliorate lung injury, and suppress inflammation and apoptosis of lung tissues. In addition, XQLD also markedly attenuated endoplasmic reticulum stress (ERS) and activated AMPK/mTOR pathway in the lung tissues of mice with AECOPD. However, the AMPK inhibitor Compound C decreased the protective effect of XQLD in AECOPD mice. Conclusion. These findings suggested that XQLD has protective effect against inflammation and apoptosis in AECOPD mice by attenuating ER stress via AMPK/mTOR pathway.

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“…Reduced pulmonary inflam-(�8,�9). Reduced pulmonary inflammation may therefore contribute to the recovery from lung injury (40,41).…”

Section: Discussionmentioning

confidence: 99%

Role of bone marrow mesenchymal stem cells in the development of PQ‑induced pulmonary fibrosis

Chen

Zhou

et al. 2019

Mol Med Report

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Paraquat (PQ) poisoning-induced pulmonary fibrosis is one of the primary causes of mortality in patients with PQ poisoning. The potential mechanism of PQ-induced pulmonary fibrosis was thought to be mediated by inflammation. Recently, bone marrow-derived mesenchymal stem cells (BMSCs) have been considered as a potential strategy for the treatment of fibrotic disease due to their anti-inflammatory and immunosuppressive effects. In the present study, an increased accumulation of BMSCs in a mouse model of PQ-induced pulmonary fibrosis following their transplantation, markedly improving the survival rate of mice with PQ poisoning. In addition, the results indicated that BMSC transplantation may inhibit the production of pro-inflammatory cytokines, including tumor necrosis factor-α interleukin (IL)-1β, IL-6 and IL-10 in the lung tissues of PQ-poisoned mice, and ultimately attenuate the pulmonary fibrosis. In vitro, BMSCs may suppress PQ-induced epithelial-to-mesenchymal transition and protect pulmonary epithelial cells from PQ-induced apoptosis. These findings suggest that BMSC transplantation may be a promising treatment for pulmonary fibrosis induced by PQ poisoning.

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Effect of Liuweibuqi Capsules in Pulmonary Alveolar Epithelial Cells and COPD Through JAK/STAT Pathway

Cited by 18 publications

References 39 publications

Activation of spinal dorsal horn P2Y<sub>13</sub> receptors can promote the expression of IL-1β and IL-6 in rats with diabetic neuropathic pain

Activation of spinal dorsal horn P2Y<sub>13</sub> receptors can promote the expression of IL-1β and IL-6 in rats with diabetic neuropathic pain

Xiaoqinglong Decoction Protects the Lungs of AECOPD Mice through the AMPK/mTOR Signaling Pathway

Role of bone marrow mesenchymal stem cells in the development of PQ‑induced pulmonary fibrosis

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Effect of Liuweibuqi Capsules in Pulmonary Alveolar Epithelial Cells and COPD Through JAK/STAT Pathway

Cited by 18 publications

References 39 publications

Activation of spinal dorsal horn P2Y<sub>13</sub> receptors can promote the expression of IL-1&beta; and IL-6 in rats with diabetic neuropathic pain

Activation of spinal dorsal horn P2Y<sub>13</sub> receptors can promote the expression of IL-1&beta; and IL-6 in rats with diabetic neuropathic pain

Xiaoqinglong Decoction Protects the Lungs of AECOPD Mice through the AMPK/mTOR Signaling Pathway

Role of bone marrow mesenchymal stem cells in the development of PQ‑induced pulmonary fibrosis

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Activation of spinal dorsal horn P2Y<sub>13</sub> receptors can promote the expression of IL-1β and IL-6 in rats with diabetic neuropathic pain

Activation of spinal dorsal horn P2Y<sub>13</sub> receptors can promote the expression of IL-1β and IL-6 in rats with diabetic neuropathic pain