The Lipocalin2 Gene is Regulated in Mammary Epithelial Cells by NFκB and C/EBP In Response to Mycoplasma

Abstract

Lcn2 gene expression increases in response to cell stress signals, particularly in cells involved in the innate immune response. Human Lcn2 (NGAL) is increased in the blood and tissues in response to many stressors including microbial infection and in response to LPS in myeloid and epithelial cells. Here we extend the microbial activators of Lcn2 to mycoplasma and describe studies in which the mechanism of Lcn2 gene regulation by MALP-2 and mycoplasma infection was investigated in mouse mammary epithelial cells. As for the LPS response of myeloid cells, Lcn2 expression in epithelial cells is preceded by increased TNFα, IL-6 and IκBζ expression and selective reduction of IκBζ reduces Lcn2 promoter activity. Lcn2 promoter activation remains elevated well beyond the period of exposure to MALP-2 and is persistently elevated in mycoplasma infected cells. Activation of either the human or the mouse Lcn2 promoter requires both NFκB and C/EBP for activation. Thus, Lcn2 is strongly and enduringly activated by mycoplasma components that stimulate the innate immune response with the same basic regulatory mechanism for the human and mouse genes.

P2X7R influences tau aggregate burden in human tauopathies and shows distinct signalling in microglia and astrocytes

“…Consistent with this, in astrocytes we found that P2X 7 R affects NFκB translocation and production of CCL2, IL-6, CXCL1 and the acute-phase protein Lcn2, all of which are downstream of NFκB ( Khorooshi et al, 2008 , Lee et al, 2012b , Liu et al, 2022 , Spooren et al, 2010 , Zhao et al, 2020 ). NFκB is increased in AD brain ( Kitamura et al, 1997 ) and pharmacological inhibition of NFκB attenuates astrocyte reactivity in APP/PS1 and 5xFAD mice ( Lindsay et al, 2021 ).…”

NOX activation in reactive astrocytes regulates astrocytic LCN2 expression and neurodegeneration

“…ROS-mediated ER stress activation in astrocytes leads to neuronal apoptosis in the METH-induced neuronal apoptosis model [ 16 ]. Several transcription factors have been identified as important regulators of LCN2 gene expression [ 5 ], including TNF-α and IL6-mediated activation of nuclear factor κB (NF-κB) and IκBζ [ 20 ]. However, how RA regulate LCN2 expression in ischemic stroke conditions remains to be established.…”

Differential transcript usage analysis of bulk and single-cell RNA-seq data with DTUrtle

“…Among the 64 selected genes are well-known cell type specific marker genes, like Cd3d and Cd3g ( T cell ), or Epcam and Lcn2 ( Zhao et al , 2020 ) ( epithelial cell ), which partially have been used in the initial cell-type assignment by the Tabula Muris Consortium. GO analysis of the selected genes revealed 12 enriched terms ( P -value < 0.01), including three T cell specific terms [‘alpha-beta T cell differentiation’ (GO:0046632), ‘positive thymic T cell selection’ (GO:0045059) and ‘negative regulation of T cell apoptotic process’ (GO:0070233)] ( Supplementary Table S1 ).…”