Journal article
Suppression of human T cell activation by derivatives of glycerol monolaurate
Scientific reports, Vol.11(1), pp.8943-8943
04/26/2021
DOI: 10.1038/s41598-021-88584-y
PMCID: PMC8076190
PMID: 33903712
Abstract
Glycerol monolaurate (GML), a naturally occurring monoglyceride, is widely used commercially for its antimicrobial properties. Interestingly, several studies have shown that GML not only has antimicrobial properties but is also an anti-inflammatory agent. GML inhibits peripheral blood mononuclear cell proliferation and inhibits T cell receptor (TCR)-induced signaling events. In this study, we perform an extensive structure activity relationship analysis to investigate the structural components of GML necessary for its suppression of human T cell activation. Human T cells were treated with analogs of GML, differing in acyl chain length, head group, linkage of acyl chain, and number of laurate groups. Treated cells were then tested for changes in membrane dynamics, LAT clustering, calcium signaling, and cytokine production. We found that an acyl chain with 12-14 carbons, a polar head group, an ester linkage, and a single laurate group at any position are all necessary for GML to inhibit protein clustering, calcium signaling, and cytokine production. Removing the glycerol head group or replacing the ester linkage with a nitrogen prevented derivative-mediated inhibition of protein cluster formation and calcium signaling, while still inhibiting TCR-induced cytokine production. These findings expand our current understanding of the mechanisms of action of GML and the of GML needed to function as a novel immunosuppressant.
Details
- Title: Subtitle
- Suppression of human T cell activation by derivatives of glycerol monolaurate
- Creators
- Micaela G. Fosdick - Roy J. and Lucille A. Carver College of MedicinePratik Rajesh Chheda - University of IowaPhuong M. Tran - Roy J. and Lucille A. Carver College of MedicineAlex Wolff - Roy J. and Lucille A. Carver College of MedicineRonal Peralta - Roy J. and Lucille A. Carver College of MedicineMichael Y. Zhang - Roy J. and Lucille A. Carver College of MedicineRobert Kerns - University of IowaJon C. D. Houtman - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.11(1), pp.8943-8943
- DOI
- 10.1038/s41598-021-88584-y
- PMID
- 33903712
- PMCID
- PMC8076190
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- Springer Nature
- Number of pages
- 11
- Grant note
- Carver College of Medicine Oberley Award from the Holden Comprehensive Cancer Center R56 AI126493 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA University of Iowa Vice President for Research P30CA086862 / National Cancer Institute of the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Department of Microbiology and Immunology at the University of Iowa
- Language
- English
- Date published
- 04/26/2021
- Academic Unit
- Microbiology and Immunology; Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry; Internal Medicine
- Record Identifier
- 9984297439502771
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