Expression and modulation of progesterone induced blocking factor (PIBF) and innate immune factors in human leukemia cell lines by progesterone and mifepristone

Leuk Lymphoma. 2007 Aug;48(8):1610-7. doi: 10.1080/10428190701471999.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimicrobial Cationic Peptides / metabolism
  • Cathelicidins
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Hormone Antagonists / pharmacology*
  • Humans
  • Interleukin-1 Receptor-Associated Kinases / metabolism
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / metabolism
  • Leukemia / drug therapy*
  • Leukemia / metabolism
  • Leukemia / pathology
  • Mifepristone / pharmacology*
  • Pregnancy Proteins / genetics
  • Pregnancy Proteins / metabolism*
  • Progesterone / pharmacology*
  • Progestins / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Suppressor Factors, Immunologic / genetics
  • Suppressor Factors, Immunologic / metabolism*
  • Toll-Like Receptor 4 / metabolism
  • Tumor Cells, Cultured / drug effects
  • alpha-Defensins / metabolism


  • Antimicrobial Cationic Peptides
  • Hormone Antagonists
  • PIBF1 protein, human
  • Pregnancy Proteins
  • Progestins
  • RNA, Messenger
  • Suppressor Factors, Immunologic
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • alpha-Defensins
  • human neutrophil peptide 1
  • human neutrophil peptide 3
  • Mifepristone
  • Progesterone
  • IRAK4 protein, human
  • Interleukin-1 Receptor-Associated Kinases
  • Cathelicidins