Propionic acid secreted from propionibacteria induces NKG2D ligand expression on human-activated T lymphocytes and cancer cells
Research output: Contribution to journal › Journal article › peer-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 language | English |
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Journal | Journal of Immunology |
Volume | 183 |
Issue number | 2 |
Pages (from-to) | 897-906 |
Number of pages | 10 |
ISSN | 0022-1767 |
DOIs | |
Publication status | Published - 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
- 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
ID: 17654243