R ole of interleukin 4 and its receptor in clinical presentation of chronic extrinsic allergic alveolitis: a pilot study

Šterclová, Martina; Matěj, Radoslav; Mandakova, Petra; Skibová, J; Vašáková, Martina

doi:10.1186/2049-6958-8-35

Cited by 8 publications

(5 citation statements)

References 29 publications

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“… 13 In broad agreement with previous studies, we also noted an air-cultured hMSC secretome contained FGFb, GM-CSF, IFNr, IL1a, IL4, IL8, IL10, IL12, MCP1, TGFb, TNFa, and VEGF which may form the basis of a minimal air-cultured hMSC secretome. 6 , 46 – 49 Similarly, IL2, IL6, IL13, MIP1a, and RANTES lay below a detectable threshold in our experimentation.…”

Section: Discussioncontrasting

confidence: 48%

“…A number of previous studies have analyzed the serum-free in vitro secretome of hMSCs. Biomolecules identified in the secretome of air-cultured hMSCs have included anti-inflammatory (IL4, IL10, IL13, and TGFb), 6 , 46 pro-inflammatory (IL2, IL12, IFNr, TNFa, and IL1a), 6 , 47 chemokines (Rantes, MCP1, IL8, and MIP1b), 6 , 48 hemopoietic (G-CSF, and GM-CSF), 6 and pleiotropic factors (IL6). 6 , 15 Substantial overlap and significant discrepancy is a key feature of hMSC secretome defining studies.…”

Section: Discussionmentioning

confidence: 99%

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Physoxia alters human mesenchymal stem cell secretome

2021

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The human mesenchymal stem cell (hMSC) secretome has pleiotropic effects which underpin their therapeutic potential. hMSC serum-free conditioned media (SFCM) has been determined to contain a variety of cytokines with roles in regeneration and suppression of inflammation. Physiological oxygen (physoxia) has been demonstrated to impact upon a number of facets of hMSC biology and we hypothesized that the secretome would be similarly modified. We tested a range of oxygen conditions; 21% O2 (air oxygen (AO)), 2% O2 (intermittent hypoxia (IH)) and 2% O2 Workstation (physoxia (P)) to evaluate their effect on hMSC secretome profiles. Total protein content of secretome was upregulated in IH and P (>3 fold vs AO) and IH (>1 fold vs P). Focused cytokine profiling indicated global upregulation in IH of all 31 biomolecules tested in comparison to AO and P with basic-nerve growth factor (bNGF) and granulocyte colony-stimulating factor (GCSF) (>3 fold vs AO) and bNGF and Rantes (>3 fold vs P) of note. Similarly, upregulation of interferon gamma-induced protein 10 (IP10) was noted in P (>3 fold vs AO). Interleukin-2 (IL2) and Rantes (in AO and P) and adiponectin, IL17a, and epidermal growth factor (EGF) (in AO only) were entirely absent or below detection limits. Quantitative analysis validated the pattern of IH-induced upregulation in vascular endothelial growth factor (VEGF), placental growth factor-1 (PIGF1), Tumor necrosis factor alpha (TNFa), IL2, IL4, and IL10 when compared to AO and P. In summary, modulation of environmental oxygen alters both secretome concentration and composition. This consideration will likely impact on delivering improved mechanistic understanding and potency effects of hMSC-based therapeutics.

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Section: Discussioncontrasting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Physoxia alters human mesenchymal stem cell secretome

2021

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“…According to our previous [ 18 , 43 ] and present studies, we suggested that TNF-α levels are indicative of lung tissue inflammation, especially in the early phases of HP, rather than fibroproliferation. On the other hand, chronic stages of HP are characterized by more pronounced fibroproliferation rather than inflammation or granuloma formation, which is represented by an overexpression of IL-4Rα, as we previously described [ 44 ]. That is probably the reason why IL- 4Rα levels did not differ among the subgroups of IIP in our current study.…”

Section: Discussionmentioning

confidence: 81%

Interstitial Score and Concentrations of IL-4Rα, PAR-2, and MMP-7 in Bronchoalveolar Lavage Fluid Could Be Useful Markers for Distinguishing Idiopathic Interstitial Pneumonias

Brůžová

Павлова²,

Matěj

et al. 2021

Diagnostics

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Idiopathic interstitial pneumonia (IIP) entails a variable group of lung diseases of unknown etiology. Idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, interstitial lung diseases related to connective tissue disease (CTD-ILD), and hypersensitivity pneumonitis (HP) can manifest with similar clinical, radiological, and histopathological features. In a differential diagnosis, biomarkers can play a significant role. We assume that levels of specific cyto- or chemokines or their receptors can signal pathogenetic processes in the lungs. Eighty patients with different types of idiopathic interstitial pneumonia were enrolled in this study. Cell counts and concentrations of tumor necrosis factor (TNF)-α, interleukin-4 receptor α, proteinase-activated receptor (PAR)-2, matrix metalloproteinase (MMP)-7, and B cell-activating factor were measured in bronchoalveolar lavage fluid using commercial ELISA kits. High resolution computer tomography results were evaluated using alveolar and interstitial (IS) score scales. Levels of TNF-α were significantly higher in HP compared to fibrosing IIP (p < 0.0001) and CTD-ILD (p = 0.0381). Concentrations of IL-4Rα, PAR-2, and MMP-7 were positively correlated with IS (p = 0.0009; p = 0.0256; p = 0.0015, respectively). Since TNF-α plays a major role in inflammation, our results suggest that HP is predominantly an inflammatory disease. From the positive correlation with IS we believe that IL-4Rα, PAR-2, and MMP-7 could serve as fibroproliferative biomarkers in differential diagnosis of IIP.

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“…Similarly, culture supernatants obtained from the BAL of chronic HP patients presented higher IL-4 and lower IFN-γ(9). Studying the IL-4/IL-4R axis may also be useful to discriminate HP from sarcoidosis, as IL-4R BAL levels appear to differ, but this requires further validation [ 81 , 82 ]. Indeed, several studies comparing cytokine levels in the BAL of HP patients with controls and/or other ILDs have been published.…”

Section: Biomarkers In Fibrotic Hpmentioning

confidence: 99%

Diagnosis of Fibrotic Hypersensitivity Pneumonitis: Is There a Role for Biomarkers?

Pereira

Fernandes

Alfaro

et al. 2023

Life

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Hypersensitivity pneumonitis is a complex interstitial lung syndrome and is associated with significant morbimortality, particularly for fibrotic disease. This condition is characterized by sensitization to a specific antigen, whose early identification is associated with improved outcomes. Biomarkers measure objectively biologic processes and may support clinical decisions. These tools evolved to play a crucial role in the diagnosis and management of a wide range of human diseases. This is not the case, however, with hypersensitivity pneumonitis, where there is still great room for research in the path to find consensual diagnostic biomarkers. Gaps in the current evidence include lack of validation, validation against healthy controls alone, small sampling and heterogeneity in diagnostic and classification criteria. Furthermore, discriminatory accuracy is currently limited by overlapping mechanisms of inflammation, damage and fibrogenesis between ILDs. Still, biomarkers such as BAL lymphocyte counts and specific serum IgGs made their way into clinical guidelines, while others including KL-6, SP-D, YKL-40 and apolipoproteins have shown promising results in leading centers and have potential to translate into daily practice. As research proceeds, it is expected that the emergence of novel categories of biomarkers will offer new and thriving tools that could complement those currently available.

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R ole of interleukin 4 and its receptor in clinical presentation of chronic extrinsic allergic alveolitis: a pilot study

Cited by 8 publications

References 29 publications

Physoxia alters human mesenchymal stem cell secretome

Physoxia alters human mesenchymal stem cell secretome

Interstitial Score and Concentrations of IL-4Rα, PAR-2, and MMP-7 in Bronchoalveolar Lavage Fluid Could Be Useful Markers for Distinguishing Idiopathic Interstitial Pneumonias

Diagnosis of Fibrotic Hypersensitivity Pneumonitis: Is There a Role for Biomarkers?

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