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Updated: Jul 9, 2025
Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
Published on: June 23, 2013
Mmp12 Is Translationally Regulated in Macrophages during the Course of Inflammation
Silvia Kuntschar1, Giulia Cardamone1, Kevin Klann2
1Institute of Biochemistry I, Faculty of Medicine, Goethe University Frankfurt, 60590 Frankfurt, Germany.
Abstract:
Despite the importance of rapid adaptive responses in the course of inflammation and the notion that post-transcriptional regulation plays an important role herein, relevant translational alterations, especially during the resolution phase, remain largely elusive. In the present study, we analyzed translational changes in inflammatory bone marrow-derived macrophages upon resolution-promoting efferocytosis. Total RNA-sequencing confirmed that apoptotic cell phagocytosis induced a pro-resolution signature in LPS/IFNγ-stimulated macrophages (Mϕ). While inflammation-dependent transcriptional changes were relatively small between efferocytic and non-efferocytic Mϕ; considerable differences were observed at the level of de novo synthesized proteins. Interestingly, translationally regulated targets in response to inflammatory stimuli were mostly downregulated, with only minimal impact of efferocytosis. Amongst these targets, pro-resolving matrix metallopeptidase 12 (Mmp12) was identified as a translationally repressed candidate during early inflammation that recovered during the resolution phase. Functionally, reduced MMP12 production enhanced matrix-dependent migration of Mϕ. Conclusively, translational control of MMP12 emerged as an efficient strategy to alter the migratory properties of Mϕ throughout the inflammatory response, enabling Mϕ migration within the early inflammatory phase while restricting migration during the resolution phase.
Insights
Macrophages use translational control to manage inflammation. Efferocytosis, or clearing dead cells, helps resolve inflammation by regulating matrix metallopeptidase 12 (MMP12) production and macrophage migration.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Post-transcriptional regulation is crucial for adaptive inflammatory responses.
- Translational alterations during inflammation resolution are not well understood.
- Macrophages (Mϕ) play key roles in inflammation and its resolution.
Purpose of the Study:
- To investigate translational changes in macrophages during the resolution phase of inflammation.
- To identify specific translationally regulated proteins involved in efferocytosis-driven resolution.
- To elucidate the role of matrix metallopeptidase 12 (MMP12) in macrophage migration during inflammation.
Main Methods:
- Analysis of translational changes in bone marrow-derived macrophages stimulated with LPS/IFNγ and undergoing efferocytosis.
- Total RNA-sequencing to confirm pro-resolution transcriptional signature.
- Quantification of de novo protein synthesis to identify translational alterations.
- Functional assays to assess the impact of MMP12 on macrophage migration.
Main Results:
- Apoptotic cell phagocytosis (efferocytosis) induced a pro-resolution signature in macrophages.
- Significant differences in de novo protein synthesis were observed between efferocytic and non-efferocytic macrophages, despite minor transcriptional changes.
- Matrix metallopeptidase 12 (MMP12) was translationally repressed during early inflammation and its translation recovered during resolution.
- Reduced MMP12 production enhanced macrophage matrix-dependent migration.
Conclusions:
- Translational control, not just transcriptional, significantly impacts macrophage function during inflammation.
- Translational regulation of MMP12 is a key mechanism controlling macrophage migration.
- This regulatory strategy allows macrophage migration during early inflammation and restricts it during resolution, aiding effective inflammatory response and resolution.
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