Simvastatin requires activation in accessory cells to modulate T-cell responses in asthma and COPD

Knobloch, Jürgen; Yakin, Yakup; Körber, Sandra; Grensemann, B; Bendella, Zeynep; Boyaci, N; Gallert, Willem-Jakob; Yanik, Sarah; Jungck, David; Koch, Andrea

doi:10.1016/j.ejphar.2016.06.037

Cited by 4 publications

(3 citation statements)

References 49 publications

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“…Leptin was also found to enhance the production of pro-inflammatory cytokines by T-cells as well as limit apoptosis in response to stress (Fujita et al, 2002 ; Lord et al, 2002 ). Simvastatin has been shown to modulate T-cell responses in models of airway inflammation such as asthma, but requires accessory cells for the observed effects (Liu et al, 2014 ; Knobloch et al, 2016 ). This modulation of adaptive immunity by statins in the context of obesity may play an important role in the observed protective effects observed in these animals.…”

Section: Discussionmentioning

confidence: 99%

Protective Capacity of Statins during Pneumonia Is Dependent on Etiological Agent and Obesity

Karlsson

Schultz‐Cherry

Rosch

2018

Front. Cell. Infect. Microbiol.

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Acute respiratory infections are a leading cause of death worldwide. Clinical data is conflicted regarding whether statins improve outcomes for pneumonia. Potential confounding factors including specific etiology of pneumonia as well as obesity could potentially mask protective benefit. Obesity is a risk factor for high cholesterol, the main target for statin therapy. We demonstrate that statin intervention conferred no protective benefit in the context of wild-type mice regardless of infectious agent. Statin intervention conferred either a protective benefit, during influenza infection, or detrimental effect, in the case of pneumococcal infection, in obese animals. These data suggest etiology of pneumonia in the context of obesity could be dramatically altered by the protective effects of statin therapy during bacterial and viral pneumonia.

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Section: Discussionmentioning

confidence: 99%

Protective Capacity of Statins during Pneumonia Is Dependent on Etiological Agent and Obesity

Karlsson

Schultz‐Cherry

Rosch

2018

Front. Cell. Infect. Microbiol.

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“…In contrast to the local innate immune cells that show an overactivation in response to respiratory pathogens in COPD [11,61], the activation process of circulating innate and adaptive immune cells appears to be rather suppressed. We have previously shown that systemic defects in Toll-like receptor signaling prevent the full activation of T-cells and monocytes in response to respiratory bacteria [9,62,63]. Here, we add the information that the suppression of the Th1-immunity might be amplified by co-morbidities in COPD.…”

Section: Discussionmentioning

confidence: 79%

“…2.5x10 5 PBMCs per approach were cultured overnight in 250 µL RPMI1640 medium (Sigma, Munich, Germany) supplemented with 10% (v/v) fetal calf serum (FCS), 2 mM L-glutamine, 100 U/mL penicillin and 100 µg/mL streptomycin (all from Sigma) at 5% CO 2 and 37 • C as described before [65]. T-cell activation and differentiation towards Th1/Tc1 in PBMCs was done as described before [63]. Briefly, PBMCs were stimulated with agonistic monoclonal anti-CD3 and anti-CD28 antibodies (500 ng/mL each; BD Bioscience, Heidelberg, Germany, cat# 555336, cat# 555725) and 10 ng/mL recombinant human IL-12 (R&D Systems, Wiesbaden, Germany, cat# 219-IL-005).…”

Section: Isolation Of Peripheral Blood Mononuclear Cells (Pbmcs)mentioning

confidence: 99%

Biomarkers for Comorbidities Modulate the Activity of T-Cells in COPD

Jameel

Gallert

Yanik

et al. 2021

IJMS

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In smoking-induced chronic obstructive pulmonary disease (COPD), various comorbidities are linked to systemic inflammation and infection-induced exacerbations. The underlying mechanisms are unclear but might provide therapeutic targets. T-cell activity is central in systemic inflammation and for infection-defense mechanisms and might be influenced by comorbidities. Hypothesis: Circulating biomarkers of comorbidities modulate the activity of T-cells of the T-helper type 1 (Th1) and/or T-cytotoxic type 1 (Tc1). T-cells in peripheral blood mononuclear cells (PBMCs) from non-smokers (NS), current smokers without COPD (S), and COPD subjects (total n = 34) were ex vivo activated towards Th1/Tc1 and were then stimulated with biomarkers for metabolic and/or cardiovascular comorbidities (Brain Natriuretic Peptide, BNP; chemokine (C-C motif) ligand 18, CCL18; C-X3-C motif chemokine ligand 1, CX3CL1; interleukin-18, IL-18) or for asthma- and/or cancer-related comorbidities (CCL22; epidermal growth factor, EGF; IL-17; periostin) each at 10 or 50 ng/mL. The Th1/Tc1 activation markers interferon-γ (IFNγ), tumor necrosis factor-α (TNFα), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were analyzed in culture supernatants by Enzyme-Linked Immunosorbent Assay (ELISA). Ex-vivo activation induced IFNγ and TNFα without differences between the groups but GM-CSF more in S vs. NS. At 10 ng/mL, the different biomarkers increased or reduced the T-cell activation markers without a clear trend for one direction in the different categories of comorbidities or for the different T-cell activation markers. At 50 ng/mL, there was a clear shift towards suppressive effects, particularly for the asthma— and cancer-related biomarkers and in cells of S and COPD. Comorbidities might suppress T-cell immunity in COPD. This could explain the association of comorbidities with frequent exacerbations.

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Simvastatin and bone marrow-derived mesenchymal stem cells (BMSCs) affects serum IgE and lung cytokines levels in sensitized mice

et al. 2019

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Simvastatin requires activation in accessory cells to modulate T-cell responses in asthma and COPD

Cited by 4 publications

References 49 publications

Protective Capacity of Statins during Pneumonia Is Dependent on Etiological Agent and Obesity

Protective Capacity of Statins during Pneumonia Is Dependent on Etiological Agent and Obesity

Biomarkers for Comorbidities Modulate the Activity of T-Cells in COPD

Simvastatin and bone marrow-derived mesenchymal stem cells (BMSCs) affects serum IgE and lung cytokines levels in sensitized mice

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