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


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


    Inflammation is an important cause of chronic obstructive pulmonary disease (COPD) and its acute exacerbation. However, the critical role of C-C chemokine receptor (CCR)1 in progression of cigarette smoke-induced chronic inflammation remains unclear. We studied CCR1 expression using immunohistochemistry, immunofluorescence, and real-time polymerase chain reaction (RT-PCR) in COPD patients and controls. Cytokine levels in peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). In vitro, we investigated Janus kinase/signal transducers and activators of transcription (JAK/STAT)/nuclear factor-κB (NF-κB) signaling in cigarette smoke extract-induced or CCR1 deficiency/overexpressed mouse macrophage cell line MH-S by RT-PCR and western blot, and measured the cytokine levels in the supernatant with ELISA. We found that CCR1 expression was upregulated in COPD patients and there was a negative correlation between CCR1 mRNA levels and predicted % forced expiratory volume in 1 min. Inflammatory cytokine levels in the peripheral blood were higher in COPD patients than controls, and these were positively correlated with CCR1 levels. CCR1 was shown to play a critical role in regulating smoke-induced inflammation via JAK/STAT3/NF-κB signaling in vitro. CCR1 may play a critical role in airway inflammation in COPD. Additionally, understanding the molecular mechanism may help develop novel methods for the treatment of COPD.



    Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and concurrent progressive airflow limitation [13]. Patients may experience episodes of exacerbated respiratory symptoms, and the frequency of exacerbations requiring hospitalization increases, resulting in significant social and economic burden and one of the major causes of morbidity and mortality worldwide [45]. The pathogenesis of COPD and exacerbations may be associated with inflammatory cells, including macrophages, neutrophils, and T lymphocytes [67]. These cells are crucial in parenchymal destruction and development of airflow limitation in patients with COPD [89].

    Chemokines and their receptors regulate leukocyte adhesion and homing, and these receptors play a critical role in trafficking of leukocytes to sites of injury and inflammation [10]. In fact, the cell surface of T cells, natural killer cells, monocytes, macrophages, lymphocytes, and neutrophils express the C-C chemokine receptor (CCR)1 [11]. Previous studies have shown that elevated blood inflammation cells, chemokine levels, and CCR1 expression are associated with increased risk of exacerbations in patients with COPD [1216]. However, the critical role of CCR1 in the progression of cigarette smoke-induced chronic inflammation remains unclear. We therefore hypothesize that CCR1 enhances airway inflammation via regulation of Janus kinase/signal transducers and activators of transcription (JAK/STAT)/nuclear factor-κB (NF-κB) signaling.

    In this study, we aimed to assess CCR1 expression in peripheral blood and bronchial tissues of patients with COPD and participants who served as controls. Furthermore, we investigated chemokine levels in plasma and correlation with lung function and CCR1 expression. We also aimed to examine the inflammatory responses of MH-S cells that overexpressed or were deficient in CCR1 expression that were treated with cigarette smoke extract (CSE). https://www.aging-us.com/article/103180/text

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    “A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This study was released back in 2018 by Oncotarget and written by various experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study mentions that “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and shares an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
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