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Published on: October 31, 2017
Long-Chain S-Acylation Is a Key Modulator During the Macrophage Inflammatory Response.
Anneroos E Nederstigt1, Samiksha Sardana1, Francine R Ianiski1
1Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, The Netherlands; Netherlands Proteomics Center, Utrecht, The Netherlands.
Molecular & Cellular Proteomics : MCP
|June 10, 2026
Summary
Long-chain S-acylation regulates macrophage inflammation. Inhibiting this process reduces inflammatory chemokines and impacts tryptophan metabolism, suggesting it as a therapeutic target for inflammatory diseases.
Area of Science:
- Biochemistry
- Immunology
- Proteomics
Background:
- Long-chain S-acylation is a critical lipid modification influencing protein function.
- Its specific role in macrophage-mediated inflammation is not fully understood.
Purpose of the Study:
- To comprehensively map the S-acylation landscape in macrophages during different activation states.
- To investigate the functional impact of S-acylation on macrophage inflammatory responses.
Main Methods:
- Utilized stable isotope labeling by amino acids in cell culture (SILAC) combined with site-specific acyl-biotin exchange (ssABE).
- Employed quantitative proteomics to analyze S-acylation patterns in THP-1 macrophages (M0 and M(LPS+ IFNɣ) states).
- Investigated the effects of pharmacological S-acylation inhibitors (2-bromopalmitate, Palmostatin B).
Main Results:
- Revealed distinct, polarization-specific S-acylation patterns in macrophages.
- Identified novel inflammation-related S-acylation sites and S-acyl peptidoforms, such as on WARS.
- Inhibition of S-acylation suppressed pro-inflammatory chemokine secretion (CXCL9, CXCL10, CCL4) and disrupted IDO1 activity.
- Palmostatin B selectively stabilized S-acylation on GPCR signaling proteins.
Conclusions:
- Long-chain S-acylation is a key regulatory mechanism in macrophage activation.
- S-acylation represents a promising therapeutic target for inflammatory diseases.
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