Dataset Information

Soluble transforming growth factor beta-1 enhances murine mast cell release of Interleukin 6 in IgE-independent and Interleukin 13 in IgE-dependent settings in vitro.

ABSTRACT:

Introduction

For immune cells transforming growth factor beta-1 (TGF-?1) can enhance or repress effector functions. Here, we characterize the effects of TGF-?1 on IgE-mediated and IL-33-mediated activation of primary murine mast cells derived from hematopoietic stem cells (bone marrow derived mast cells; BMMC). We also investigated potential interactions between TGF-?1 and stem cell factor (SCF). We conclude TGF-?1 plays a selectively stimulatory role for mast cell cultures in vitro.

Methods

BMMCs from C57BL/6 mice were differentiated with IL-3 and then treated with TGF-?1. BMMCs were exposed to TGF-?1, primed with IgE, activated with antigen, and then IL-6 and IL-13 cytokine release was quantified using ELISA. Additionally, the effects of TGF-?1 on both IgE and IL-33-mediated short term activation were observed via flow cytometric analysis of both surface LAMP-1 expression and intracellular IL-6. Receptor colocalization was visualized using fluorescence confocal microscopy and individual receptor expression levels were also quantified.

Results

Resting IL-6 production increased with TGF-?1 but significance was lost following BMMC activation via IgE receptor (Fc?RI) crosslinking. This was similar to a comparison effect due to SCF treatment alone, which also enhanced resting levels of IL-6. TGF-?1 treatment enhanced release of IL-13 only with Fc?RI-IgE-mediated activation. TGF-?1 suppressed mobilization of IL-6 with short-term BMMC activation when stimulated with IL-33. Lastly, colocalization patterns of the SCF receptor (CD117) and Fc?RI with IgE crosslinking were unaffected by TGF-?1 treatment, but individual expression levels for Fc?RI, CD117, and TGF?RII were all reduced following either IgE activation or TGF-?1 treatment; this reduction was partially recovered in BMMCs that were both activated by IgE and treated with TGF-?1.

Discussion

These data reveal a novel positive effect of soluble TGF-?1 on mast cell activation in vitro, suggesting mast cells may be activated through a non-canonical pathway by TGF-?1. Understanding this interaction will provide insight into the potential role of mast cells in settings where TGF-?1 is produced in an aberrant manner, such as in and around high grade tumors.

SUBMITTER: Lyons DO

PROVIDER: S-EPMC6239331 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Soluble transforming growth factor beta-1 enhances murine mast cell release of Interleukin 6 in IgE-independent and Interleukin 13 in IgE-dependent settings in vitro.

Lyons David O DO Plewes Michele R MR Pullen Nicholas A NA

PloS one 20181116 11

<h4>Introduction</h4>For immune cells transforming growth factor beta-1 (TGF-β1) can enhance or repress effector functions. Here, we characterize the effects of TGF-β1 on IgE-mediated and IL-33-mediated activation of primary murine mast cells derived from hematopoietic stem cells (bone marrow derived mast cells; BMMC). We also investigated potential interactions between TGF-β1 and stem cell factor (SCF). We conclude TGF-β1 plays a selectively stimulatory role for mast cell cultures in vitro.<h4> ...[more]

PMID: 30444930

Similar Datasets

Project description:Mast cells (MCs) are granular cells of the innate immune system which develop from CD34+/CD117+ progenitors and play a role in orchestrating adaptive immune responses. They have a well-known role in allergic reactions following immunoglobulin (Ig)E-mediated activation of the cell-surface expressed IgE high-affinity receptor (Fc?RI). MCs can also respond to various other stimuli due to the expression of a variety of receptors including toll-like receptors (TLRs), immunoglobulin (IgG) receptors (Fc?R), complement receptors such as C5a (CD88) expressed by skin MCs, neuropeptides receptors including nerve growth factor receptor, (NGFR), cytokines receptors such as (IL)-1R and IL-3R, and chemokines receptors including CCR-1 and CCR-3. MCs release three groups of mediators upon degranulation differentiated according to their chemical composition, storage, and time to release. These include preformed mediators (mainly histamine, tryptase, and chymase), de novo synthesized mediators such as prostaglandin (PG)D2, leukotriene (LT)B4 and LTD4, and cytokines including IL-1?, IL-3, tumor necrosis factor (TNF)?, and transforming growth factor(TGF)-?. Emerging evidence indicates a role for IgE-independent MC activation in the late-stage asthmatic response as well as in non-allergic airway diseases including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and lung cancer. MC infiltration/activation has been reported in some, but not all, studies of lung cancer. MC-derived TNF-? possesses tumor-suppressive activity while IL-1? supports tumor progression and metastasis. In IPF lungs, an increase in density of tryptase- and chymase-positive MCs (MCTC) and overexpression of TGF-? support the fibrosis progression. MC-derived chymase activates latent TGF-? that induces the differentiation of fibroblasts to matrix-producing myofibroblasts. In summary, increasing evidence highlights a critical role of MCs in non-allergic diseases that may indicate new approaches for therapy.

Dataset Information

Soluble transforming growth factor beta-1 enhances murine mast cell release of Interleukin 6 in IgE-independent and Interleukin 13 in IgE-dependent settings in vitro.

Introduction

Methods

Results

Discussion

Publications

Soluble transforming growth factor beta-1 enhances murine mast cell release of Interleukin 6 in IgE-independent and Interleukin 13 in IgE-dependent settings in vitro.

Similar Datasets

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