Expression and modulation of progesterone induced blocking factor (PIBF) and innate immune factors in human leukemia cell lines by progesterone and mifepristone.
Srivastava. Maya D MD; Thomas. Anil A; Srivastava. B I S BI; Check. Jerome H JH
Key Findings
- All tested leukemia cell lines had PIBF mRNA, but only four showed PIBF protein","Progesterone increased PIBF and LL‑37 (and other innate immune factors) in those cells","Mifepristone (RU486) reduced PIBF and LL‑37 expression"]
- practical_outcomes
- :
- For biohackers
- the data hint that progesterone might enhance innate immune peptides like LL‑37
- but there
- s no clear dosage or protocol for healthy individuals. More human studies are needed before recommending hormone use for immune or longevity benefits."
Summary
The study shows that progesterone can boost the production of the immune‑modulating protein PIBF and the antimicrobial peptide LL‑37 in certain leukemia cell lines, while the drug mifepristone does the opposite. This suggests hormones can affect innate immunity, but the work was done in cancer cells in a lab, not in healthy people.
Abstract
Progesterone (P), required for successful pregnancy, influences autoimmune, infectious, and malignant diseases via adaptive and innate immune effects. P induces NK inhibitor progesterone induced blocking factor (PIBF) in CD8+ T cells. PIBF isoforms could permit solid tumor immune escape. Expression and modulation of PIBF and innate immune proteins by P in leukemia cells and leukocyte subpopulations have not been reported. Ten T, seven myeloid, six B, five epithelial, fibroblast BG9, G-CSF mobilized CD34+ stem cells, and peripheral blood mononuclear cells were screened for PIBF mRNA by RT-PCR, and protein by immunohistochemistry in SRIK-NKL, MOT, U937, HL60, R-CLL, MD-E, 729pH6neo, SRIH-B(ATL), SRIK-B(T-PLL), and MeWo. Cell lines expressing PIBF and exemplifying myeloid/monoblast, natural killer/T, and B lineages were cultured with and without 0.5 - 5 microM P or 0.5 - 0.05 microM mifepristone (RU486) for 24 h. Subsequently they were examined for changes in the expression of mRNA by RT-PCR and protein by immunohistochemistry for PIBF and some innate immune factors. All cells expressed PIBF mRNA; protein only in four (SRIK-NKL, U937, SRIK-B(T-PLL) and HL60) out of 10 cell lines tested. P increased and RU486 decreased PIBF in U937, SRIK-B(T-PLL) and SRIK-NKL. P upregulated TLR-4 in U937, and HNP1 - 3, LL-37, IRAK-2, and IRAK-4 in multiple lines and RU486 down regulated these. PIBF may be used by some leukemias to evade immune surveillance and is a potential therapeutic target. P may impact infection and autoimmunity via effects on LPS receptor, TLR signaling, and antimicrobial peptides.
Study Information
pubmed
2007
2007-01-01T00:00:00.000Z
10.1080/10428190701471999
64
38