TGF-β, but not IL-4, polarized macrophages induce fibrotic responses in lung fibroblasts
TGF-β-polarized macrophages promote fibrotic responses in lung fibroblasts, while IL-4-polarized macrophages do not.
Where it sits
this study against the rest of the pe 22-28 corpusSummary and findings
This study assessed the effects of IL-4- and TGF-β-polarized macrophages on fibrotic responses in normal human lung fibroblasts (NHLFs). Coculture with TGF-β-polarized macrophages induced α-smooth muscle actin levels in NHLFs, while IL-4-polarized macrophages did not. The findings suggest a role for TGF-β signaling in promoting fibrosis.
Abstract
<title>Abstract</title> <p> <bold>Introduction</bold> Macrophages are implicated in the initiation and regulation of pulmonary fibrosis, where anti-inflammatory macrophages promote fibrosis. Interleukin-4 (IL-4) and Transforming Growth Factor (TGF)-β stimulation of naïve macrophages results in the polarization to anti-inflammatory macrophages which are often used for mechanistic <italic>in vitro</italic> studies of fibrotic properties of these cells. <bold>Aims</bold> To assess the effect of IL-4- and TGF-β-polarized macrophages on fibrotic responses of normal human lung fibroblasts (NHLFs) in order to identify the most appropriate anti-inflammatory macrophage subset for use in <italic>in vitro</italic> model systems. <bold>Methods</bold> Peripheral blood mononuclear cells, human THP-1 monocytes and B-cell precursor leukemia cells were stimulated with IL-4 or TGF-β to induce anti-inflammatory macrophage polarization. Naïve macrophages were used as control. Whole-genome transcriptomes were analysed using RNA-sequencing. NHLFs were cocultured with polarized macrophages derived from THP-1, and conditioned medium transfer experiments were performed. Fibrotic responses were assessed by immunofluorescence. Size exclusion columns were used to separate the conditioned medium on molecular weight. TGF-β receptor kinase inhibitor RepSox was used to block TGF-β pathway signaling in NHLFs. <bold>Results</bold> Coculture with TGF-β-, but not IL-4-polarized macrophages, induced α-smooth muscle actin (αSMA) levels in NHLFs. Conditioned medium from TGF-β-, but not IL-4-, polarized macrophages induced αSMA, collagen and fibronectin protein levels in NHLFs. Size exclusion experiments revealed that the profibrotic effect remained intact in the conditioned medium fraction containing proteins larger than 100kD. Subsequent RNA-sequencing analysis showed increased expression of several potential high molecular weight profibrotic proteins related to TGF-β signaling pathway activation in TGF-β polarized macrophages. Pretreatment of NHLFs with RepSox blocked the profibrotic response of NHLFs induced by conditioned medium from TGF-β-polarized macrophages. <bold>Conclusion</bold> TGF-β-polarized macrophages promoted fibrotic responses of NHLFs, whereas IL-4-polarized macrophages did not; the profibrotic activity of TGF-β-polarized macrophages is mediated through activation of TGF-β signaling pathway in NHLFs. </p>
Background
The study appears to investigate the role of macrophage polarization by TGF-β and IL-4 in inducing fibrotic responses in lung fibroblasts. Understanding how different cytokines influence macrophage behavior could be crucial for developing therapies for fibrotic lung diseases. The specific focus on TGF-β and IL-4 suggests an interest in distinguishing their effects on fibrosis.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Without access to the abstract or full text, it is unclear how the findings compare to existing literature or their clinical significance. The title suggests a differential role of TGF-β and IL-4 in macrophage-induced fibrosis, but details are lacking.
Limitations
- Not reported in abstract.