The interplay of DAMPs, TLR4, and proinflammatory cytokines in pulmonary fibrosis

Bolourani, Siavash; Brenner, Max; Wang, Haichao

doi:10.1007/s00109-021-02113-y

Cited by 61 publications

(25 citation statements)

References 175 publications

(198 reference statements)

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“…These findings suggested that CCL3 plays an important role in pulmonary inflammation and PF, and that DHA inhibits CCL3 expression to attenuate pulmonary inflammatory responses and PF. fibroblasts, leading to the formation of fibrosis [25]. Furthermore, many cytokines, particularly the IL-6 family, can activate STAT3 rapidly within cells.…”

Section: Discussionmentioning

confidence: 99%

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Dihydroartemisinin attenuates pulmonary inflammation and fibrosis in rats by suppressing JAK2/STAT3 signaling

You

Jiang

Zhang

et al. 2022

Aging

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Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has induced a worldwide pandemic since early 2020. COVID-19 causes pulmonary inflammation, secondary pulmonary fibrosis (PF); however, there are still no effective treatments for PF. The present study aimed to explore the inhibitory effect of dihydroartemisinin (DHA) on pulmonary inflammation and PF, and its molecular mechanism. Morphological changes and collagen deposition were analyzed using hematoxylin-eosin staining, Masson staining, and the hydroxyproline content. DHA attenuated early alveolar inflammation and later PF in a bleomycin-induced rat PF model, and inhibited the expression of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNFα), and chemokine (C-C Motif) Ligand 3 (CCL3) in model rat serum. Further molecular analysis revealed that both pulmonary inflammation and PF were associated with increased transforming growth factor-β1 (TGF-β1), Janus activated kinase 2 (JAK2), and signal transducer and activator 3(STAT3) expression in the lung tissues of model rats. DHA reduced the inflammatory response and PF in the lungs by suppressing TGF-β1, JAK2, phosphorylated (p)-JAK2, STAT3, and p-STAT3. Thus, DHA exerts therapeutic effects against bleomycin-induced pulmonary inflammation and PF by inhibiting JAK2-STAT3 activation. DHA inhibits alveolar inflammation, and attenuates lung injury and fibrosis, possibly representing a therapeutic candidate to treat PF associated with COVID-19.

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Section: Discussionmentioning

confidence: 99%

“…Cytokines can either directly activate myofibroblasts or induce the transformation of epithelial cells into fibroblasts, leading to the formation of fibrosis [ 25 ]. Furthermore, many cytokines, particularly the IL-6 family, can activate STAT3 rapidly within cells.…”

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin attenuates pulmonary inflammation and fibrosis in rats by suppressing JAK2/STAT3 signaling

You

Jiang

Zhang

et al. 2022

Aging

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“…Particularly in the lungs, cells release DAMPs to alert the innate immune system to begin cell death. In addition, heat shock proteins and high-mobility group Box 1 stimulate mitogen-activated protein kinases and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) to activate the inflammatory response (Bolourani et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Post-COVID-19 Syndrome

et al. 2022

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Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many individuals have reported persistent symptoms and/or complications lasting beyond 4 weeks, which is now called post-COVID-19 syndrome. SARS-CoV-2 is a respiratory coronavirus that causes COVID-19, and injury to the lungs is expected; however, there is often damage to numerous other cells and organs, leading to an array of symptoms. These long-term symptoms occur in patients with mild to severe COVID-19; currently, there is limited literature on the potential pathophysiological mechanisms of this syndrome.Objectives: The purpose of this integrative review is to summarize and evaluate post-COVID-19 syndrome from a biological perspective.Methods: An integrative review was conducted using Whittemore and Knafl's methodology for literature published through August 30, 2021. The PubMed, CINAHL, and Web of Science databases were searched for articles published as of August 30, 2021, using combinations of the following key words: post-COVID-19 syndrome, post-SARS-CoV-2, long COVID-19, long COVID-19 syndrome, and pathophysiology of post-COVID-19. Data were analyzed using the constant comparison method.Results: The search generated 27,929 articles. After removing duplicates and screening abstracts and full-text reviews, we retained 68 articles and examined 54 specific articles related to the pathophysiology of post-COVID-19 syndrome. The findings from our review indicated that there were four pathophysiological categories involved: virus-specific pathophysiological variations, oxidative stress, immunologic abnormalities, and inflammatory damage.Discussion: Although studies examining the pathophysiology of post-COVID-19 syndrome are still relatively few, there is growing evidence that this is a complex and multifactorial syndrome involving virus-specific pathophysiological variations that affect many mechanisms but specifically oxidative stress, immune function, and inflammation. Further research is needed to elucidate the pathophysiology, pathogenesis, and longer term consequences involved in post-COVID-19 syndrome.

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“…Due to viral infection, systemic inflammation, and coagulation disturbance, tissues are constantly damaged, releasing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), including the extracellular molecule adenosine triphosphate (ATP) [ 19 , 38 , 39 ]. Extracellular ATP acts through paracrine and autocrine signaling pathways, acting as a strong “find me” signal for immune cell recruitment to damaged sites [ 40 ].…”

Section: Introductionmentioning

confidence: 99%

Purinergic signaling elements are correlated with coagulation players in peripheral blood and leukocyte samples from COVID-19 patients

2022

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For over a year, the coronavirus disease 2019 has been affecting the world population by causing severe tissue injuries and death in infected people. Adenosine triphosphate (ATP) and the nicotinamide adenine dinucleotide (NAD +) are two molecules that are released into the extracellular microenvironment after direct virus infection or cell death caused by hyper inflammation and coagulopathy. Also, these molecules are well known to participate in multiple pathways and have a pivotal role in the purinergic signaling pathway. Thus, using public datasets available on the Gene Expression Omnibus (GEO), we analyzed raw proteomics data acquired using mass spectrometry (the gold standard method) and raw genomics data from COVID-19 patient samples obtained by microarray. The data was analyzed using bioinformatics and statistical methods according to our objectives. Here, we compared the purinergic profile of the total leukocyte population and evaluated the levels of these soluble biomolecules in the blood, and their correlation with coagulation components in COVID-19 patients, in comparison to healthy people or non-COVID-19 patients. The blood metabolite analysis showed a stage-dependent inosine increase in COVID-19 patients, while the nucleotides ATP and ADP had positive correlations with fibrinogen and other coagulation proteins. Also, ATP, ADP, inosine, and hypoxanthine had positive and negative correlations with clinical features. Regarding leukocyte gene expression, COVID-19 patients showed an upregulation of the P2RX1, P2RX4, P2RX5, P2RX7, P2RY1, P2RY12, PANX1, ADORA2B, NLPR3, and F3 genes. Yet, the ectoenzymes of the canonical and non-canonical adenosinergic pathway (ENTPD1 and CD38) are upregulated, suggesting that adenosine is produced by both active adenosinergic pathways. Hence, approaches targeting these biomolecules or their specific purinoreceptors and ectoenzymes may attenuate the high inflammatory state and the coagulopathy seen in COVID-19 patients.

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The interplay of DAMPs, TLR4, and proinflammatory cytokines in pulmonary fibrosis

Cited by 61 publications

References 175 publications

Dihydroartemisinin attenuates pulmonary inflammation and fibrosis in rats by suppressing JAK2/STAT3 signaling

Dihydroartemisinin attenuates pulmonary inflammation and fibrosis in rats by suppressing JAK2/STAT3 signaling

Post-COVID-19 Syndrome

Purinergic signaling elements are correlated with coagulation players in peripheral blood and leukocyte samples from COVID-19 patients

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