title: 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.
authors: Division of Allergy and Immunology, The Cleveland Clinic, Cleveland, OH, USA. mdsrivastava@aol.com
authors: Maya D
authors: MD
authors: Srivastava
authors: Anil
authors: A
authors: Thomas
authors: B I S
authors: BI
authors: Srivastava
authors: Jerome H
authors: JH
authors: Check
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015735:Mifepristone / Q000494:pharmacology*; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013491:Suppressor Factors, Immunologic / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D023084:alpha-Defensins / Q000378:metabolism; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D006727:Hormone Antagonists; C110058:PIBF1 protein, human; D011257:Pregnancy Proteins; D011372:Progestins; D012333:RNA, Messenger; D013491:Suppressor Factors, Immunologic; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; C406427:human neutrophil peptide 3; D015735:Mifepristone; D011374:Progesterone; C507773:IRAK4 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; D054804:Cathelicidins