Propionic acid secreted from propionibacteria induces NKG2D ligand expression on human-activated T lymphocytes and cancer cells

Research output: Contribution to journalJournal articlepeer-review

We found that propionic acid secreted from propionibacteria induces expression of the NKG2D ligands MICA/B on activated T lymphocytes and different cancer cells, without affecting MICA/B expression on resting peripheral blood cells. Growth supernatant from propionibacteria or propionate alone could directly stimulate functional MICA/B surface expression and MICA promoter activity by a mechanism dependent on intracellular calcium. Deletion and point mutations further demonstrated that a GC-box motif around -110 from the MICA transcription start site is essential for propionate-mediated MICA promoter activity. Other short-chain fatty acids such as lactate, acetate, and butyrate could also induce MICA/B expression. We observed a striking difference in the molecular signaling pathways that regulate MICA/B. A functional glycolytic pathway was essential for MICA/B expression after exposure to propionate and CMV. In contrast, compounds with histone deacetylase-inhibitory activity such as butyrate and FR901228 stimulated MICA/B expression through a pathway that was not affected by inhibition of glycolysis, clearly suggesting that MICA/B is regulated through different molecular mechanisms. We propose that propionate, produced either by bacteria or during cellular metabolism, has significant immunoregulatory function and may be cancer prophylactic.
Original languageEnglish
JournalJournal of Immunology
Volume183
Issue number2
Pages (from-to)897-906
Number of pages10
ISSN0022-1767
DOIs
Publication statusPublished - 2009

Bibliographical note

Keywords: Bacteria; Calcium; Cell Line, Tumor; Hematologic Neoplasms; Histocompatibility Antigens Class I; Humans; Jurkat Cells; Ligands; Lymphocyte Activation; NK Cell Lectin-Like Receptor Subfamily K; Promoter Regions, Genetic; Propionic Acids; T-Lymphocytes; Transcriptional Activation

    Research areas

  • Bacteria, Calcium, Cell Line, Tumor, Hematologic Neoplasms, Histocompatibility Antigens Class I, Humans, Jurkat Cells, Ligands, Lymphocyte Activation, NK Cell Lectin-Like Receptor Subfamily K, Promoter Regions, Genetic, Propionic Acids, T-Lymphocytes, Transcriptional Activation

ID: 17654243