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Fredriksson, Karin; Lundahl, Joachim; Palmberg, Lena; Romberger, Debra J.; Liu, X. D.; Rennard, Stephen I.; Sköld, C. Magnus

doi:10.1023/a:1023274532456

Cited by 17 publications

(5 citation statements)

References 29 publications

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“…Very few studies have determined the content or activity of RBC conditioned media. One study reported that T cell proliferation was stimulated in the presence of RBC conditioned media and that this stimulation was comparable with intact RBC-mediated proliferation 23 and another observed that culturing fibroblasts in the presence of intact RBCs or RBC conditioned media stimulated the secretion of IL-8 and the expression of the corresponding mRNA 8 . This result was also replicated by culturing fibroblasts in the presence of TNF-α and IL-1β, both of which were cytokines detected in the RBC conditioned media in this current study (Fig.…”

Section: Discussionmentioning

confidence: 91%

“…The concentrations of released cytokines are summarised in the Supplementary results (Supplementary Table S3 – S4 ). Analysis of RBC conditioned media has not been widely reported in the scientific literature, but its effect on T cells and fibroblasts has been briefly reported 8 , 23 . However, the cytokine profile of the conditioned media in these studies was not investigated.…”

Section: Resultsmentioning

confidence: 99%

“…As such, after blood collection, the plasma level of MIF could be significantly altered by relatively low levels of haemolysis. In addition, RBCs, or soluble factors released by these cells, can also stimulate the secretion of pro-inflammatory markers from lung fibroblasts 8 . These studies demonstrate that RBCs may be an important component of the immune system and are capable of signalling or receiving signal from other cell types.…”

Section: Introductionmentioning

confidence: 99%

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Red blood cells are dynamic reservoirs of cytokines

Karsten

Breen

Herbert

2018

Sci Rep

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Red blood cells (RBCs) have been shown to affect immune function and can induce inflammatory responses after transfusion. The transfusion of washed RBCs can significantly reduce adverse effects, however, the soluble factors that may mediate these effects have not been identified. Previous studies have identified, but not quantified, a small number of chemokines associated with RBCs. We isolated RBCs from healthy volunteers and quantified of a panel of 48 cytokines, chemokines, and growth factors in the lysate, cytosol, and conditioned media of these cells using Luminex® technology. This analysis revealed that, after correcting for white blood cell and platelet contamination, 46 cytokines were detected in RBC lysates, and the median concentration in RBCs was 12-fold higher than in the plasma. In addition, extensive washing of RBCs, such as that performed in proteomics analyses or prior to some RBC transfusions, significantly attenuated the release of six cytokines following incubation at 37 °C. This supports the hypothesis that, alongside its gas exchange function, RBCs play a role in cytokine signalling. This discovery may help supplement disease biomarker research and may shed light on adverse inflammatory processes that can follow RBC transfusion.

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Section: Discussionmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Red blood cells are dynamic reservoirs of cytokines

Karsten

Breen

Herbert

2018

Sci Rep

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“…Myodifferentiation and fibrosis are particularly important in airway remodeling and asthma as they can lead to exacerbated symptoms and progressive damage (Grinnell, 2000; Hinz et al, 2007). To better understand how fibroblasts are affected by soluble factors from other types of cells in airway remodeling, researchers have conducted mixed coculture (embedding additional cell types into the fibroblasts-laden collagen), conditioned media coculture (feeding fibroblast-laden gel matrix with supernatants collected from other types of cells), and segregated Transwell coculture CGC experiments (Fredriksson et al, 2003; Zagai et al, 2007; Margulis et al, 2009; Wygrecka et al, 2013). These studies revealed that mast cells, red blood cells, and eosinophils can promote fibroblast contraction in mixed 3D coculture, or in conditioned media culture through paracrine signaling; whereas blood monocytes and lung epithelial cells attenuate fibroblast-mediated gel contractility, an important aspect of tissue repair (Sköld et al, 2000; Epa et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Investigating Fibroblast-Induced Collagen Gel Contraction Using a Dynamic Microscale Platform

Zhang

Day

et al. 2019

Front. Bioeng. Biotechnol.

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Mechanical forces have long been recognized as fundamental drivers in biological processes, such as embryogenesis, tissue formation and disease regulation. The collagen gel contraction (CGC) assay has served as a classic tool in the field of mechanobiology to study cell-induced contraction of extracellular matrix (ECM), which plays an important role in inflammation and wound healing. In a conventional CGC assay, cell-laden collagen is loaded into a cell culture vessel (typically a well plate) and forms a disk-shaped gel adhering to the bottom of the vessel. The decrement in diameter or surface area of the gel is used as a parameter to quantify the degree of cell contractility. In this study, we developed a microscale CGC assay with an engineered well plate insert that uses surface tension forces to load and manipulate small volumes (14 μL) of cell-laden collagen. The system is easily operated with two pipetting steps and the microscale device moves dynamically as a result of cellular forces. We used a straightforward one-dimensional measurement as the gel contraction readout. We adapted a conventional lung fibroblast CGC assay to demonstrate the functionality of the device, observing significantly more gel contraction when human lung fibroblasts were cultured in serum-containing media vs. serum-free media ( p ≤ 0.05). We further cocultured eosinophils and fibroblasts in the system, two important cellular components that lead to fibrosis in asthma, and observed that soluble factors from eosinophils significantly increase fibroblast-mediated gel contraction ( p ≤ 0.01). Our microscale CGC device provides a new method for studying downstream ECM effects of intercellular cross talk using 7- to 35-fold less cell-laden gel than traditional CGC assays.

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“…In this context, fibroblasts respond vigorously to the early inflammatory response mediators IL-1β and TNF-α 28,29. These mediators induce a number of responses in fibroblasts including release of the cytokines IL-6,10 IL-8,30 and MMPs 16. Thus, fibroblasts may participate in the amplification of IL-1β and TNF-α-induced inflammation.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory effects of budesonide in human lung fibroblasts are independent of histone deacetylase 2

Wang¹,

Nelson²,

Weiler³

et al. 2013

JIR

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Objective and designReduced expression of histone deacetylase 2 (HDAC2) in alveolar macrophages and epithelial cells may account for reduced response of chronic obstructive pulmonary disease (COPD) patients to glucocorticoids. HDAC2 expression and its role in mediating glucocorticoid effects on fibroblast functions, however, has not been fully studied. This study was designed to investigate whether HDAC2 mediates glucocorticoid effects on release of inflammatory cytokines and matrix metalloproteinases (MMPs) from human lung fibroblasts.MethodsHuman lung fibroblasts (HFL-1 cells) were stimulated with interleukin (IL)-1 β plus tumor necrosis factor (TNF)-α in the presence or absence of the glucocorticoid budesonide. Cytokines (IL-6 and IL-8) were quantified by enzyme linked immunosorbent assay (ELISA) and MMPs (MMP-1 and MMP-3) by immunoblotting in culture medium. The role of HDAC2 was investigated using a pharmacologic inhibitor as well as a small interfering ribonucleic acid (siRNA) targeting HDAC2.ResultsWe have demonstrated that budesonide concentration-dependently (10−10–10−7 M) inhibited IL-6, IL-8, MMP-1, and MMP-3 release by HFL-1 cells in response to IL-1β plus TNF-α. While an HDAC inhibitor significantly blocked the inhibitory effect of budesonide on human bronchial epithelial cells (HBECs) and monocytes (THP-1 cells), it did not block the inhibitory effect of budesonide on release of cytokines and MMPs from HFL-1 cells. Similarly, an HDAC2-siRNA blocked budesonide inhibition of cytokine release in HBECs, but it did not block the inhibitory effect of budesonide on HFL-1 cytokine and MMP release. Furthermore, budesonide significantly blocked release of cytokines and MMPs to a similar degree in normal and COPD lung fibroblasts as well as in HFL-1 cells exposed or not exposed to cigarette smoke extract.ConclusionThese findings suggest that, in contrast to airway epithelial cells and monocytes/macrophages, HDAC2 is not required for budesonide to inhibit MMP and cytokine release by lung fibroblasts and this inhibitory pathway appears to be intact in cultured fibroblasts from COPD patients. These results also suggest that budesonide has the potential to modulate fibroblast-mediated tissue remodeling following airway inflammation in COPD, which is mediated via an HDAC2 independent pathway.

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Untitled

Cited by 17 publications

References 29 publications

Red blood cells are dynamic reservoirs of cytokines

Red blood cells are dynamic reservoirs of cytokines

Investigating Fibroblast-Induced Collagen Gel Contraction Using a Dynamic Microscale Platform

Anti-inflammatory effects of budesonide in human lung fibroblasts are independent of histone deacetylase 2

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