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

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.
AuthorsMaya D Srivastava, Anil Thomas, B I S Srivastava, Jerome H Check
JournalLeukemia & lymphoma (Leuk Lymphoma) Vol. 48 Issue 8 Pg. 1610-7 (Aug 2007) ISSN: 1042-8194 [Print] England
PMID17701593 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • 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
  • CAP18 lipopolysaccharide-binding protein
  • Mifepristone
  • Progesterone
  • IRAK4 protein, human
  • Interleukin-1 Receptor-Associated Kinases
Topics
  • Antimicrobial Cationic Peptides (metabolism)
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Hormone Antagonists (pharmacology)
  • Humans
  • Interleukin-1 Receptor-Associated Kinases (metabolism)
  • Killer Cells, Natural (drug effects, metabolism)
  • Leukemia (drug therapy, metabolism, pathology)
  • Mifepristone (pharmacology)
  • Pregnancy Proteins (genetics, metabolism)
  • Progesterone (pharmacology)
  • Progestins (pharmacology)
  • RNA, Messenger (genetics, metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Suppressor Factors, Immunologic (genetics, metabolism)
  • Toll-Like Receptor 4 (metabolism)
  • Tumor Cells, Cultured (drug effects)
  • alpha-Defensins (metabolism)

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