Cigarette smoke-induced lung inflammation in COPD mediated via CCR1/JAK/STAT /NF-κB pathway

Zhao, Kaishun; Dong, Ran; Yu, Yanfang; Tu, Chunlin; Liu, Ying; Cui, YuJuan; Bao, Lei; Ling, Chunhua

doi:10.18632/aging.103180

Cited by 28 publications

(22 citation statements)

References 39 publications

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“…There is limited evidence showing that both cigarette smoke and influenza infection can upregulate CCR1 expression [ 40 , 41 ]. In addition, few publications could show a role of CCR1 in lung injury using models of lung fibrosis [ 42 , 43 ], and as far as we know, there is just one publication showing an anti-inflammatory effect of CCR1 pharmacological blockade in a model of lung inflammation triggered by cigarette smoke [ 41 ]. On the other hand, as we are showing here, others also demonstrated a relevant anti-inflammatory effect of CCR5 pharmacological blockade in several models of lung injury in mice [ 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice

et al. 2021

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Influenza A virus (IAV) infection is a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Since macrophage inflammatory protein 1 α, a chemokine that acts through CC-chemokine receptor (CCR)-5, appears elevated in COPD patients’ airways, we evaluated whether CCR5 antagonist Maraviroc could inhibit the exacerbated lung inflammatory response noted after IAV H1N1 infection in mice exposed to cigarette smoke (Cs). C57BL/6 mice, subjected or not to Cs inhalation for 11 days, were infected with H1N1 at day 7. Maraviroc (10 mg/kg) or dexamethasone (1 mg/kg) were given in a therapeutic schedule, followed by the analyses of lung function, survival rate, and inflammatory changes. As compared to mice subjected to Cs or H1N1 alone, the insult combination significantly worsened airway obstruction, neutrophil infiltration in the airways, and the survival rate. All changes were sensitive to Maraviroc but not dexamethasone. Maraviroc also reduced the accumulation of neutrophils and macrophages as well as CXCL1 production in the lung tissue, and serum levels of IL-6, whereas comparable viral titers in the lungs were noted in all infected groups. Collectively, these findings suggest that Maraviroc oral treatment could be an effective therapy for controlling acute exacerbations of respiratory diseases such as COPD.

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Section: Discussionmentioning

confidence: 99%

CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice

et al. 2021

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“…2B). They can activate the JAK-signal transducer and activator of transcription (STAT) pathway [8][9][10][11][12][13][14][15][16][17][18]. They were also related to the function of monocytes, T cells, and neutrophils.…”

Section: Resultsmentioning

confidence: 99%

“…CCR1 and CR1 play critical roles in the process of inflammation. CCR1 was involved in the regulation of smoke-induced inflammation via JAK/STAT3 signaling [15]. CCR1 may also play a role in macrophage and endothelial cell infiltration in experimental arthritis models partly through activating JAK signaling [16].…”

Section: Discussionmentioning

confidence: 99%

JAK signaling was involved in the pathogenesis of Polymyalgia Rheumatica

Yang

et al. 2022

Preprint

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Objectives. Polymyalgia Rheumatica (PMR) is a common inflammatory disease in elderly persons whose pathogenesis is unclear. We aimed to explore the pathogenetic features of PMR and find a new therapeutic strategy. Methods. We included 11 patients with PMR and 20 age-matched and sex-matched healthy controls (HC) in this study. The disease features were described. The gene expression profiles were analyzed in peripheral blood mononuclear cells (PBMCs) by RNA sequencing and were confirmed by RT-PCR. We also tested gene expression profiles in five patients with PMR after tofacitinib therapy. Results. Patients with PMR experienced pain with high disease activity scores. The gene expression of PBMCs in patients with PMR differed from that in HC by RNA sequencing. GO and KEGG analysis demonstrated that inflammatory response and cytokine-cytokine receptor interaction were the most remarkable pathways. There were markedly expanded IL6R, IL1B, IL1R1, JAK2, TLR2, TLR4, TLR8, CCR1, CR1, S100A8, S100A12, and IL17RA expressions. Those genes may trigger the JAK signaling. Furthermore, tofacitinib, a pan JAK inhibitor, effectively treated five patients with PMR, leading to clinical remission and a significant decrease in inflammatory genes. Conclusions. Many inflammatory genes associated with JAK signaling were increased in patients with PMR, suggesting an important role of JAK signaling in PMR disease development. JAK inhibitors may effectively treat PMR. Keywords: Polymyalgia Rheumatica, Inflammatory pathway, JAK signaling

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“…During inflammation, cytokines play an important role. Many cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1 beta (IL-1β), could activate the Janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, contributing the overexpression of numerous pro-inflammatory factors in the lung 17 – 19 . So, the JAK/STAT pathway is involved in COPD pathogenesis, and its inhibitors might be a potential treatment for COPD.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of salmeterol and magnesium isoglycyrrhizinate combination treatment in rats with chronic obstructive pulmonary disease

Yang

Huang

Tian

et al. 2022

Sci Rep

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The most classic treatment recommended in the current chronic obstructive pulmonary disease (COPD) guidelines is glucocorticoid and β2 receptor agonist combination, such as salmeterol xinafoate and fluticasone propionate (Sal/Flu), causing many adverse reactions due to hormones. Magnesium isoglycyrrhizinate (MgIG) is an anti-inflammatory glycyrrhizic acid preparation for treating chronic inflammation, contributing to its structure is similar to steroidal anti-inflammatory drugs. In this study, we successfully established COPD rat model by endotracheal-atomized lipopolysaccharide exposure and cigarette smoke induction, as characterized by lung function decline. We discovered that salmeterol xinafoate/MgIG combination could alleviated lung inflammation infiltration, airway wall thickness (AWT) and the secretion of bronchial mucin MUC5AC of COPD rats more than salmeterol xinafoate, MgIG, or salmeterol xinafoate and fluticasone propionate treatment did, as well as reduced inflammatory cells (white blood cells, neutrophils and lymphocytes) accumulation in bronchoalveolar lavage fluid and decreased TNF-α, IL-6 and IL-1β production in the serum of COPD rats. Finally, we found that Moreover, the mechanism involved might be related to the suppression of JAK/STAT signaling pathway. Overall, our studies suggested that MgIG might be a potential alternative adjuvant drug for fluticasone propionate for the clinical treatment of patients with COPD.

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Cigarette smoke-induced lung inflammation in COPD mediated via CCR1/JAK/STAT /NF-κB pathway

Cited by 28 publications

References 39 publications

CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice

CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice

JAK signaling was involved in the pathogenesis of Polymyalgia Rheumatica

Efficacy of salmeterol and magnesium isoglycyrrhizinate combination treatment in rats with chronic obstructive pulmonary disease

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