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

Abstract

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.

Simple, low-cost, and well-performing method, the outgrowth technique, for the isolation of epithelial cells from nasal polyps

“…Epithelial cell function was assessed by the production of typical cytokines of type 2 inflammation, representatively IL-33 and periostin. Concentrations of IL33 and periostin in culture supernatants were measured by ELISA according to the manufacturer’s instructions (Invitrogen, cat #: BMS2048TEN, Carlsbad, CA, USA; R&D Systems, cat #: DY3548B, Minneapolis, MN, USA) and as described previously [10]. To obtain the supernatants, 5,000 cells were seeded in a 24-well plate with 1 ml BEGM, and medium was renewed every 2 days until 70%–80% confluence.…”

Simple, low-cost, and well-performing method, the outgrowth technique, for the isolation of cells from nasal polyps

“…Epithelial cell function was assessed by the production of typical cytokines of type 2 inflammation, representatively IL-33 and periostin. Concentrations of IL33 and periostin in culture supernatants were measured by ELISA according to the manufacturer’s instructions (Invitrogen, cat #: BMS2048TEN, Carlsbad, CA, USA; R&D Systems, cat #: DY3548B, Minneapolis, MN, USA) and as described previously [ 21 ]. To obtain the supernatants, 5,000 cells were seeded in a 24-well plate with 1 ml BEGM, and medium was renewed every 2 days until 70%–80% confluence.…”

Therapeutic Effects and Molecular Mechanisms of Bioactive Compounds Against Respiratory Diseases: Traditional Chinese Medicine Theory and High-Frequency Use

“…IL-8 recruits neutrophils and secretes several neutrophil elastases and metalloproteases, e.g., MMP-9, which results in alveolar destruction. GM-CSF and IL-6 contribute to the increase in airway smooth muscle mass and proliferation, leading to bronchial obstruction (Knobloch et al, 2018;Jamal Jameel et al, 2021). Human airway smooth muscle cells (HASMCs) contributing to the secretion of cytokines and chemokines are related to non-type 2 airway inflammation and remodeling processes in COPD (Knobloch et al, 2013;Knobloch et al, 2016;Knobloch et al, 2019).…”