Genomic organization of the gene coding for human pre-B-cell colony enhancing factor and expression in human fetal membranes

Abstract

Pre-B-cell colony enhancing factor (PBEF) was first isolated from an activated peripheral blood lymphocyte cDNA library and was found to be involved in the maturation of B-cell precursors. It was subsequently identified as one of the genes upregulated by distending the human fetal membranes in vitro. Here we report on the genomic organization of this gene, which is composed of 11 exons and 10 introns, spanning 34·7 kb of genomic DNA. Neither the gene nor the protein has any homology with other cytokines in any currently available database. The use of two promoters (proximal and distal) may result in differential, tissue specific expression of the PBEF transcripts. The 5 -flanking region lacks the classical sequence motif that would place it with the hematopoietic cytokines; however, it has several putative regulatory elements, suggesting that this gene may be chemically and mechanically responsive to inducers of transcription.The three PBEF mRNA transcripts were observed in both normal and infected human fetal membranes but were significantly upregulated (P<0·05) in severe infection. The PBEF protein was immunolocalized, in both normal and infected tissues, to both the normal fetal cells of the amnion and chorion and the maternal decidua of the membranes, and to the invading neutrophils. These stained strongly and were likely to contribute to the increased expression in infection. The amniotic epithelial cell line (WISH cells) has been used as a model to study PBEF gene modulation. Lipopolysaccharide, interleukin (IL)-1 , tumour necrosis factor (TNF) and IL-6 all significantly increased the expression of PBEF in 4 h of treatment. The addition of dexamethasone to IL-1 and TNF significantly reduced the response of PBEF to these cytokines. IL-8 treatment failed to alter PBEF gene expression. Thus PBEF is a cytokine expressed in the normal fetal membranes and upregulated when they are infected. It is likely to have a central role in the mechanism of infection-induced preterm birth.

NAMPT overexpression in prostate cancer and its contribution to tumor cell survival and stress response

“…Chronic inflammation in the prostate gland, which produces reactive oxygen species, is an important etiological factor for prostate carcinogenesis (Nelson et al, 2003;De Marzo et al, 2007). Intriguingly, NAMPT is an inflammation-response gene, and its expression increases in multiple inflammatory tissues (Ognjanovic et al, 2001;Ye et al, 2005;Busso et al, 2008). That NAMPT expression is elevated early in prostate neoplasia suggests NAMPT may have a role in the etiology of prostate cancer.…”

Maternal Leptin, Adiponectin, Resistin, Visfatin and Tumor Necrosis Factor-Alpha in Normal and Gestational Diabetes

“…Thus, elevated maternal visfatin concentrations in GDM at 2nd trimester may reflect an impairment of visfatin function in target tissues, dysregulation of biosynthesis, or a response to hyperglycemia [52]. On the other hand, TNF-a is known to enhance visfatin expression in human placental cells [53]. Thus, the placenta could be a source of increased visfatin in GDM.…”

Target validation for genomics using peptide‐specific phage antibodies: A study of five gene products overexpressed in colorectal cancer

“…The biological relevance of overexpression of PBEF in CRC is unclear given the reported normal function of PBEF is in the maturation of B cell precursors. 20 More recent studies have shown the upregulation of PBEF in infected fetal membranes 22,23 and specific localization to normal fetal cells and also to invading neutrophils. 23 The PBEF gene contains multiple promotor sites responsive to different transcription inducing agents 23 that may account for differential expression of the protein in different tissues and also possibly differences in function.…”