Immunohistochemical Expression Analysis of the Human Interferon-Inducible Gene IFI16, a Member of the HIN200 Family, Not Restricted to Hematopoietic Cells

Abstract

This is the first description of an extensive immunohistochemical analysis of interferon (IFN)-inducible gene IFI16 expression in normal tissues. Immunohistochemical detection of IFI16 in paraffin-embedded tissues is achieved by using a polyclonal antibody raised against its C-terminal fragment that recognizes its three closely migrating isoforms in Western blotting. The results clearly indicate that IFI16 expression is not restricted to the hematopoietic compartment. In normal adult human tissues, it is prominent in stratified squamous epithelia and particularly intense in parabasal cells in the proliferating compartments, but it gradually decreases in the more differentiated suprabasal layers. Understanding of IFI16 expression in vivo is essential for interpretation of the results obtained from in vitro studies and elucidation of its physiologic role. The constitutive expression and wider distribution of IFI16 in normal human tissues, not restricted to the hematopoietic compartment, strongly support the possibility of an important role in cell differentiation that can be further modulated by other stimuli, such as IFN. 815

Role of IFI 16, a member of the interferon-inducible p200-protein family, in prostate epithelial cellular senescence

“…Recent immunohistochemical analyses of IFI 16 protein in normal human tissues revealed that its expression is not restricted to hematopoietic cells (Gariglio et al, 2002;Wei et al, 2003). Additionally, hybridization of IFI 16 cDNA probe to a multiple tissue Northern blot revealed that IFI 16 mRNA expression is relatively high in several human tissues, including the prostate (Wei et al, 2003).…”

“…The protein IFI 16 is primarily nuclear in lymphoid cells (Dawson and Trapani, 1995). Importantly, recent analyses of IFI 16 expression in several human tissues by immunohistochemistry revealed that expression of IFI 16 is not restricted to cells of hematopoietic origin (Gariglio et al, 2002;Wei et al, 2003). Of note, IFN induction of IFI 16 in hematopoietic cells appears to be cell-type-and donor-specific (Schlaak et al, 2002).…”

The interferon-inducible IFI16 gene inhibits tube morphogenesis and proliferation of primary, but not HPV16 E6/E7-immortalized human endothelial cells

“…Immunohistochemical analysis demonstrated that IFI16 is highly expressed in endothelial cells, suggesting that it may be involved in angiogenesis [28,29]. When HUVEC are maintained at subconfluent density in complete medium, they proliferate and are highly sensitive to growth arrest by contact inhibition.…”

“…By contrast, only some resident macrophages were stained and granulocytes were negative. In addition, in normal adult human tissues, IFI16 is expressed in a highly restricted pattern in selected cells within certain organs [28,29]. Prominent IFI16 expression is seen in stratified squamous epithelia, particularly intense in basal cells in the proliferating compartments, whereas it gradually decreases in the more differentiated suprabasal compartment.…”

The interferon‐inducible gene IFI16 secretome of endothelial cells drives the early steps of the inflammatory response

“…In addition to partially conserved repeat motifs of 200 amino acids, designated A, B and C, the IFI16 protein contains a DAPIN/PYRIN domain within its N-terminus [6,7]. This domain was identified as a putative protein-protein interaction domain at the N-terminus of several other proteins believed to function in inflammatory signalling pathways.…”