4-Hydroxybutyrate Promotes Endogenous Antimicrobial Peptide Expression in Macrophages

Catalina Pineda Molina, George S Hussey, Jonas Eriksson, Michael A Shulock, Laura L Cárdenas Bonilla, Ross M Giglio, Riddhi M Gandhi, Brian M Sicari, Derek Wang, Ricardo Londono, Denver M Faulk, Neill J Turner, Stephen F Badylak
Tissue Engineering: Part A. Vol 25, 9 & 10
Link to Publication: https://pubmed.ncbi.nlm.nih.gov/30982430/

Abstract

This study evaluated the biological activity of hydroxylated derivatives of butyrate as inductors of antimicrobial peptides (AMPs) in murine bone marrow-derived macrophages in vitro. A differential modulation of AMP expression by the hydroxylated derivatives of butyrate is shown. The ability of sodium 4-hydroxybutyrate to upregulate AMP expression through a histone deacetylase inhibitory-independent mechanism, and to promote increased resistance to bacterial contamination in vivo are also shown. The findings provide an alternative for prevention of bacterial contamination of implanted biomaterials. Functionalization of biomaterials with hydroxylated derivatives of butyrate can enhance the endogenous antimicrobial activity of the immune system through increased production of AMPs by host cells, thus providing protection against bacterial contamination.

Impact Statement

This study evaluated the biological activity of hydroxylated derivatives of butyrate as inductors of antimicrobial peptides (AMPs) in murine bone marrow-derived macrophages in vitro. A differential modulation of AMP expression by the hydroxylated derivatives of butyrate is shown. The ability of sodium 4-hydroxybutyrate to upregulate AMP expression through a histone deacetylase inhibitory-independent mechanism, and to promote increased resistance to bacterial contamination in vivo are also shown. The findings provide an alternative for prevention of bacterial contamination of implanted biomaterials. Functionalization of biomaterials with hydroxylated derivatives of butyrate can enhance the endogenous antimicrobial activity of the immune system through increased production of AMPs by host cells, thus providing protection against bacterial contamination.

Authors and Funding

C.P.M. was supported by the Colciencias-Fulbright Scholarship and the Tuition Remission Fellowship (TRF) from The Center for Latin American Studies (CLAS), University of Pittsburgh. The authors thank Lori Walton from the Histology Center at the McGowan Institute for Regenerative Medicine for histological section preparation. Partial funding of this study was provided by Becton, Dickinson and Company/CR Bard, Inc.