transforming-growth-factor-beta and Pneumonia--Viral

Topics: Coronavirus Infections; COVID-19; Fibrosis; Humans; Immunotherapy; Inflammation; Lung; Pandemics; Pneumonia, Viral; Transforming Growth Factor beta

Pudilan (PDL), a four-herb prescription with the traditional function of heat-clearing and detoxifying, has been clinically used as an anti-SARS-CoV-2 infectory agent in China. PDL might also have therapeutic potentials for COVID-19 while the underlying mechanisms remain to be clarified.. We used network pharmacology analysis and selected 68 co-targeted genes/proteins as targets of both PDL and COVID-19. These co-targeted genes/proteins were predicted by SwissDock Server for their high-precision docking simulation, and analyzed by STRING for proteins to protein interaction (PPI), pathway and GO (gene ontology) enrichment. The therapeutic effect for PDL treatment on COVID-19 was validated by the TCMATCOV (TCM Anti COVID-19) platform.. PDL might prevent the entrance of SARS-CoV-2 entry into cells by blocking the angiotensin-converting enzyme 2 (ACE2). It might inhibit the cytokine storm by affecting C-reactive protein (CRP), interferon-γ (IFN-γ), interleukin- 6 (IL-6), interleukin- 10 (IL-10), tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), C-C motif chemokine ligand 5 (CCL5), transforming growth factor-β1 (TGFβ1), and other proteins. PDL might moderate the immune system to shorten the course of the disease, delay disease progression, and reduce the mortality rate.. PDL might have a therapeutic effect on COVID-19 through three aspects, including the moderate immune system, anti-inflammation, and anti-virus entry into cells.

Topics: Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Drugs, Chinese Herbal; Humans; Immunologic Factors; Interferon-gamma; Interleukins; Molecular Docking Simulation; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Protein Interaction Maps; SARS-CoV-2; Transforming Growth Factor beta; Virus Internalization

Topics: Betacoronavirus; China; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drugs, Chinese Herbal; Humans; Medicine, Chinese Traditional; Molecular Docking Simulation; Pandemics; Phytotherapy; Pneumonia, Viral; Protein Interaction Maps; SARS-CoV-2; Transforming Growth Factor beta

Topics: Alveolar Epithelial Cells; Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Betacoronavirus; Coronavirus Infections; COVID-19; Host Microbial Interactions; Humans; Lung; Pandemics; Peptide Fragments; Peptidyl-Dipeptidase A; Pneumonia, Viral; Pulmonary Fibrosis; Receptors, Coronavirus; Receptors, Virus; Renin-Angiotensin System; SARS-CoV-2; Transforming Growth Factor beta

The outbreak of the highly contagious and deadly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease 2019 (COVID-19), has posed a serious threat to public health across the globe, calling for the development of effective diagnostic markers and therapeutics. Here, we report a highly reliable severity diagnostic biomarker, acetylated 676th lysine transforming growth factor-beta-induced protein (TGFBIp K676Ac). TGFBIp K676Ac was consistently elevated in the blood of patients with SARS-CoV-2 pneumonia (

Topics: Acetylation; Antibodies, Neutralizing; Betacoronavirus; Biomarkers; Case-Control Studies; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Extracellular Matrix Proteins; Gene Expression; Humans; Intensive Care Units; Leukocyte Count; Leukocytes, Mononuclear; Lung; Lysine; NF-kappa B; Pandemics; Pneumonia, Viral; Primary Cell Culture; Prognosis; Protein Processing, Post-Translational; Respiratory Insufficiency; SARS-CoV-2; Severity of Illness Index; Transforming Growth Factor beta

The immunological mechanisms underlying the clinical presentation of SARS-CoV-2 infection and those influencing the disease outcome remain to be defined. Myeloid-derived suppressor cells (MDSC) have been described to be highly increased during COVID-19, however, their role remains elusive. We performed an in depth analysis of MDSC in 128 SARS-CoV-2 infected patients. Polymorphonuclear (PMN)-MDSC expanded during COVID-19, in particular in patients who required intensive care treatments, and correlated with IL-1β, IL-6, IL-8, and TNF-α plasma levels. PMN-MDSC inhibited T-cells IFN-γ production upon SARS-CoV-2 peptides stimulation, through TGF-β- and iNOS-mediated mechanisms, possibly contrasting virus elimination. Accordingly, a multivariate regression analysis found a strong association between PMN-MDSC percentage and fatal outcome of the disease. The PMN-MDSC frequency was higher in non-survivors than survivors at the admission time, followed by a decreasing trend. Interestingly, this trend was associated with IL-6 increase in non-survivors but not in survivors. In conclusion, this study indicates PMN-MDSC as a novel factor in the pathogenesis of SARS-CoV2 infection, and open up to new therapeutic options.

Topics: Aged; Area Under Curve; Betacoronavirus; Coronavirus Infections; COVID-19; Female; Humans; Interferon-gamma; Interleukin-1beta; Interleukin-6; Male; Middle Aged; Myeloid-Derived Suppressor Cells; Neutrophils; Nitric Oxide Synthase Type II; Pandemics; Peptides; Pneumonia, Viral; Proportional Hazards Models; ROC Curve; SARS-CoV-2; Survival Rate; T-Lymphocytes; Transforming Growth Factor beta

The COVID-19 fatality rate is high when compared to the H1N1pdm09 (pandemic Influenza A virus H1N1 subtype) rate, and although both cause an aggravated inflammatory response, the differences in the mechanisms of both pandemic pneumonias need clarification. Thus, our goal was to analyze tissue expression of interleukins 4, 13, (IL-4, IL-13), transforming growth factor-beta (TGF-β), and the number of M2 macrophages (Sphingosine-1) in patients who died by COVID-19, comparing with cases of severe pneumopathy caused by H1N1pdm09, and a control group without lung injury. Six lung biopsy samples of patients who died of SARS-CoV-2 (COVID-19 group) were used and compared with ten lung samples of adults who died from a severe infection of H1N1pdm09 (H1N1 group) and eleven samples of patients who died from different causes without lung injury (CONTROL group). The expression of IL-4, IL-13, TGF-β, and M2 macrophages score (Sphingosine-1) were identified through immunohistochemistry (IHC). Significantly higher IL-4 tissue expression and Sphingosine-1 in M2 macrophages were observed in the COVID-19 group compared to both the H1N1 and the CONTROL groups. A different mechanism of diffuse alveolar damage (DAD) in SARS-CoV-2 compared to H1N1pdm09 infections were observed. IL-4 expression and lung remodeling are phenomena observed in both SARS-CoV-2 and H1N1pdm09. However, SARS-CoV-2 seems to promote lung damage through different mechanisms, such as the scarce participation Th1/Th17 response and the higher participation of the Th2. Understanding and managing the aggravated and ineffective immune response elicited by SARS-CoV-2 merits further clarification to improve treatments propose.

Topics: Aged; Aged, 80 and over; Biomarkers; Coronavirus Infections; COVID-19; Female; Humans; Interleukin-13; Interleukin-4; Lung; Macrophages; Male; Middle Aged; Pandemics; Pneumonia, Viral; Sphingosine; Transforming Growth Factor beta

Lower respiratory viral infections, such as influenza virus and severe acute respiratory syndrome coronavirus 2 infections, often cause severe viral pneumonia in aged individuals. Here, we report that influenza viral pneumonia leads to chronic nonresolving lung pathology and exacerbated accumulation of CD8

Topics: Age Factors; Animals; CD8-Positive T-Lymphocytes; COVID-19; Host-Pathogen Interactions; Humans; Immunologic Memory; Influenza, Human; Lung; Mice, Inbred C57BL; Orthomyxoviridae; Orthomyxoviridae Infections; Pandemics; Pneumonia, Viral; SARS-CoV-2; Transforming Growth Factor beta

To gain further insights in the pathogenesis of herpesvirus pneumonia in allogeneic bone marrow transplant recipients, transplanted mice (B10.BR --> CBA) with graft-versus-host disease (GVHD) and control mice (transplanted mice without GVHD and normal CBA mice) were infected intranasally with herpes simplex virus type 1 (HSV-1). When compared with infected control mice, infected allogeneic transplant recipients with GVHD showed increased periluminal mononuclear cell infiltrates. However, infected allogeneic transplant recipients with GVHD showed lower virus content in the lung tissue than infected control mice. High concentrations of transforming growth factor-beta 1 (TGF-beta1) were detected in the bronchoalveolar lavage (BAL) fluid of mock-infected allogeneic transplant recipients with GVHD, which increased slightly after infection. Anti-TGF-beta treatment of allogeneic transplant recipients with GVHD significantly decreased the histological evidence of pneumonitis at day 4 after HSV-1 infection. We conclude that allogeneic transplant recipients with GVHD have (1) increased pneumonia, (2) highly elevated levels of TGF-beta1 in the BAL fluid, and (3) reduced pulmonary virus content after HSV-1 infection. Our data suggest that the newly recognized dysregulation of cytokine (TGF-beta1) production may be more important than the viral load for the increased severity of HSV-1 pneumonia in allogeneic transplant recipients with GVHD.

Topics: Animals; Bone Marrow Transplantation; Bronchoalveolar Lavage Fluid; Female; Graft vs Host Disease; Herpes Simplex; Lung; Mice; Mice, Inbred CBA; Pneumonia; Pneumonia, Viral; Radiation Chimera; Simplexvirus; Transforming Growth Factor beta; Transplantation, Homologous

Acute inflammation in the lung is characterized by a phase of tissue injury followed by a phase of tissue repair. When the latter is excessive, fibrosis occurs. Alveolar macrophages (AM) can produce cytokines involved in both phases of acute lung inflammation, notably interleukin-6 (IL-6), involved in injury and transforming growth factor-beta (TGF-beta), mediating repair. We hypothesized that AM were activated in both phases, and studied IL-6 and TGF-beta production by AM during complications of lung transplantation, acute rejection (AR), and cytomegalovirus pneumonitis (CMVP). In addition, we analyzed these cytokines in bronchiolitis obliterans (BO), a fibrotic complication of lung transplantation linked to previous AR and CMVP. At the onset of AR and CMVP, IL-6 secretion increased, whereas AM TGF-beta content was increased, but not its secretion. In contrast, with time, IL-6 reached control value whereas TGF-beta secretion rose significantly. In BO, IL-6 was not oversecreted, but TGF-beta increased, notably before functional abnormalities occurred. These results show that during acute complications of lung transplantation, AM display an early activation with oversecretion of IL-6, which is involved in tissue injury, counterbalanced by a late activation in which TGF-beta predominates, mediating tissue repair. The results provide new insights into the pathogenesis of BO, which is linked to acute complications of lung transplantation through this biphasic AM activation.

Topics: Adolescent; Adult; Bronchiolitis Obliterans; Bronchoalveolar Lavage Fluid; Child; Cytomegalovirus Infections; Female; Graft Rejection; Humans; Immunohistochemistry; Interleukin-6; Lung; Lung Transplantation; Macrophages, Alveolar; Male; Middle Aged; Pneumonia, Viral; Postoperative Complications; Transforming Growth Factor beta