The Mechanism of the Inhibitory Effect of Progesterone on Lymphocyte Cytotoxicity: I. Progesterone‐Treated Lymphocytes Release a Substance Inhibiting Cytotoxicity and Prostaglandin Synthesis

Abstract

Progesterone-treated lymphocytes (generator lymphocytes) of healthy pregnant women release a nondialyzable factor that inhibits both cytotoxic activity and prostaglandin F2 alpha synthesis of test lymphocytes. Production of this factor is blocked by protein synthesis inhibitors (cycloheximide and actinomycin D). Sodium dodecylsulfate polyacrylamide electrophoresis of the partially purified material revealed a main 34,000 MW protein band. Progesterone-treated lymphocytes of pregnant women showing clinical symptoms of threatened preterm delivery (risk group) failed to release this substance.

Identification of a novel chromosome region, 13q21.33-q22.2, for susceptibility genes in familial chronic lymphocytic leukemia

“…However, no conserved splice site or coding mutations were identified in this gene. PIBF1 is a lymphocyte-secreted immunomodulatory molecule 41 that is expressed in spleen 35 and overexpressed in breast tumor cell lines. 42 PIBF1 is a microtubuleassociated protein that localizes to centrosomes, 42 where abnormalities are frequently observed in cancer cells, although their role in tumorigenesis is unknown.…”

PIBF (progesterone induced blocking factor) is overexpressed in highly proliferating cells and associated with the centrosome

“…13 PIBF was originally described as a 34 kDa protein. 1 Expression cloning with antibodies generated against this secreted form identified a transcript corresponding to a 90 kDa protein encoded by 18 exons 5 that seems to be the predominant PIBF mRNA form. In Western blot analyses using PIBF-specific antibodies, we consistently detected an approximately 90 kDa protein, which represented the dominant PIBF protein form in all tissues and cell lines tested.…”

“…1 However, previous protein expression studies revealed that PIBF was also expressed by the progesterone receptor positive human mammary carcinoma cell line, MCF-7. 5 An extensive BLAST search analysis of the cloned PIBF mRNA sequence using the human dEST library database (http://www.ncbi.nlm.nih.gov/ BLAST, est_human database) suggested a more universal expression and revealed that PIBF mRNA is expressed not only in lymphocytes but also in many other cell types, mainly in embryonic tissues, pregnant uterus, placenta and testis (ϳ 30% of all entries).…”

“…1 PIBF exerts immunosuppressive effects by inhibiting NK cell activity, polarizing immune responses towards TH2 dominance and downregulating effector cytokine responses. [1][2][3][4] Recently, evidence has emerged that PIBF is expressed by malignant cells as it was detected in the culture supernatant of the human mammary carcinoma cell line MCF-7 upon induction with insulin. 5 This suggests that PIBF produced by a tumor cell line might be secreted similarly to pregnancy or activated lymphocytes in culture.…”

Progesterone-induced blocking factor differentially regulates trophoblast and tumor invasion by altering matrix metalloproteinase activity

“…Previously we reported that Progesterone-Induced Blocking Factor (PIBF) is secreted by maternal lymphocytes and mediates the immunological effects of progesterone during pregnancy [4,5]. PIBF inhibits Natural Killer (NK) cell activity and enhances Th2-type cytokine production via the JAK1/STAT6 and PKC/Ca++ pathways [6,7], thus supports the maintenance of pregnancy.…”