Impaired Host Defense in Mice Lacking ONZIN

Abstract

ONZIN is a small, cysteine-rich peptide of unique structure that is conserved in all vertebrates examined to date. We show that ONZIN is expressed at high levels in epithelial cells of the intestinal tract, the lung, and in cells of the immune system including macrophages and granulocytes. Because this pattern of expression is suggestive of a role in innate immune function, we have generated mice lacking this protein and examined their ability to respond to challenge with infectious agents. Onzin−/− mice show a heightened innate immune response after induction of acute peritonitis with Klebsiella pneumoniae. This increased response is consistent with an increased bacterial burden in the Onzin−/− mice. Ex vivo studies show that, whereas phagocytosis is not altered in Onzin−/− neutrophils, phagocytes lacking this protein kill bacteria less effectively. This result identifies ONZIN as a novel class of intracellular protein required for optimal function of the neutrophils after uptake of bacteria.

The downregulation of onzin expression by PKCɛ-ERK2 signaling and its potential role in AML cell differentiation

“…18 However, both the basis for the differential expression of onzin and its function remain greatly elusive. Here, we provide the first demonstration that two leukemic cell differentiationinducing agents ATRA and especially PMA significantly inhibited the expression of onzin in AML cell lines and primary cells as well as some onzin-expressing solid tumor cells.…”

Excess PLAC8 promotes an unconventional ERK2-dependent EMT in colon cancer

“…In poorly differentiated carcinomas where it was overexpressed, PLAC8 frequently showed cytosolic distribution ( Figure 1, F and H). It will be instructive to examine the localization of PLAC8 protein in adipocytes and dendritic cells given its role in brown fat differentiation and immune function (3)(4)(5).…”

“…Subsequently, Plac8 mRNA expression was observed in myeloid and lymphoid cells, as well as in epithelial cells in the lung and intestine (3). Plac8-deficient mice have defects in innate immunity (3) and exhibit contact hypersensitivity (4), impaired brown and white fat differentiation, and late-onset obesity (5,6). In addition, Plac8 transcripts are upregulated in immortalized mouse colonocytes transformed by combined mutant H-ras and p53 (7).…”

“…By in situ hybridization (ISH), Plac8 expression is highly expressed in giant trophoblasts and the spongiotrophoblast layer in mouse placenta (2). Subsequently, Plac8 mRNA expression was observed in myeloid and lymphoid cells, as well as in epithelial cells in the lung and intestine (3). Plac8-deficient mice have defects in innate immunity (3) and exhibit contact hypersensitivity (4), impaired brown and white fat differentiation, and late-onset obesity (5,6).…”

PLAC8 Localizes to the Inner Plasma Membrane of Pancreatic Cancer Cells and Regulates Cell Growth and Disease Progression through Critical Cell-Cycle Regulatory Pathways

“…PLAC8, also known as onzin, is a small protein ($16 kDa) that was originally described to be highly expressed in mouse placenta (4,5). PLAC8 mRNA expression has subsequently also been detected in myeloid and lymphoid cells as well as lung and intestinal epithelial cells (6). Plac8 deficiency in mice has been described to result in defects in innate immunity (6), impaired brown and white fat differentiation as well as late onset obesity (7,8), and contact hypersensitivity (9).…”