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Turkish Journal of Biology

Abstract

Background/aim: Antimicrobial peptides (AMPs) are small peptides involved in host defense and have been widely studied for their roles in innate immunity against microbial pathogens. Mesenchymal stem cells (MSCs), which provide stromal support in tissues such as bone marrow, are also capable of secreting AMPs, although the signaling pathways controlling this function remain unclear. The present study investigates the role of the aryl hydrocarbon receptor (AHR) signaling, a xenobiotic response pathway, in AMP production by MSCs.

Materials and methods: To assess AMP activation, human MSCs were stimulated with the agonist FICZ and antagonist SR1. TNF-α + IL-1β and LPS were used as inflammatory controls. The expression of the AMP genes cathelicidin antimicrobial peptide (CAMP/LL-37), lipocalin 2 (LCN2), surfactant protein D (SFTPD), and defensin beta 4A (DEFB4A) was quantitatively analyzed. Escherichia coli (E.coli) was cultured in conditioned media from MSCs and antimicrobial activity was evaluated using bacterial growth kinetics, optical density measurements, and colony-forming unit assays. Antimicrobial metabolites present in the conditioned media were identified and characterized using GC-MS-based profiling.

Results: Stimulating MSCs increased the expression of selected AMP-associated genes in response to different conditions. E. coli cultures exposed to the media showed reduced viability and alterations in bacterial cell division dynamics. Single-colony assays confirmed reduced colony formation in all groups other than the TNF-α + IL-1β group. Untargeted GC-MS-based metabolomic analysis revealed stimulus-specific differences in extracellular metabolites with reported antimicrobial activity, including the saturated fatty acids myristic acid and palmitic acid and the organic acid oxalic acid under AHR-modulating conditions.

Conclusion: MSCs modulate AMP-associated responses to AHR activation and inflammatory conditions. AHR signaling partially overlaps with inflammation-induced AMP/metabolite responses. These findings suggest that the antibacterial activity of MSCs may involve both AMP-associated transcriptional changes and stimulus-dependent shifts in extracellular metabolites.

Author ORCID Identifier

CANSU ÖZDEMİR SAKA: 0000-0003-4095-7475

BEYZA TURGUT: 0009-0000-1560-8631

CEREN TUNCAY: 0009-0003-6075-6520

CEMİL CAN EYLEM: 0000-0002-3353-2869

EMİRHAN NEMUTLU: 0000-0002-7337-6215

DOI

10.55730/1300-0152.2980

Keywords

Antimicrobial peptides, mesenchymal stem cells, inflammation, aryl hydrocarbon receptor pathway, metabolomics

First Page

364

Last Page

376

Publisher

The Scientific and Technological Research Council of Türkiye (TÜBİTAK)

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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