ZBP-89, Sp1, and Nuclear Factor-κB Regulate Epithelial Neutrophil-activating Peptide-78 Gene Expression in Caco-2 Human Colonic Epithelial Cells

ABSTRACT Persistent infection with Pseudomonas aeruginosaincreases interleukin-8 (IL-8) levels and causes dense neutrophil infiltrations in the airways of patients with chronic airway diseases. Recently, we have reported that nitrite reductase from P. aeruginosa induces the production of IL-8 in respiratory cells, including bronchial epithelial cells. To determine the molecular mechanism(s) of nitrite reductase-induced IL-8 expression in respiratory cells, A549 epithelial cells were transfected with plasmids containing serial deletions of the 5′-flanking region of the IL-8 gene and then exposed to nitrite reductase. Nitrite reductase significantly enhanced IL-8 gene promoter-driven reporter activity. This increased IL-8 gene expression was inhibited by mutating the nuclear factor-κB (NF-κB) binding element. Nitrite reductase enhanced nuclear localization of the NF-κB binding complex. Furthermore, nitrite reductase induced the degradation of IκBα, the major cytoplasmic inhibitor of NF-κB, and the expression of IκBα mRNA. These data support the critical role of the activation of NF-κB in nitrite reductase-induced IL-8 gene expression in airway epithelium.

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Role of nuclear factor‐κB (NF‐κB) in the regulation of pro‐inflammatory IκB‐kinase‐ε (IKKε) gene expression in human pulmonary epithelial cells

The FASEB Journal ◽

10.1096/fasebj.2021.35.s1.04957 ◽

2021 ◽

Vol 35 (S1) ◽

Author(s):

Amandah Necker‐Brown ◽

Andrew Thorne ◽

Akanksha Bansal ◽

Mahmoud Mostafa ◽

Anthony Gerber ◽

...

Keyword(s):

Gene Expression ◽

Epithelial Cells ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Pulmonary Epithelial Cells ◽

Iκb Kinase

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Analysis of Septin 9 gene expression in laser microdissected colonic epithelial cells along the colorectal adenoma-carcinoma sequence

Zeitschrift für Gastroenterologie ◽

10.1055/s-0031-1278467 ◽

2011 ◽

Vol 49 (05) ◽

Author(s):

A Kalmár ◽

K Tóth ◽

S Spisák ◽

O Galamb ◽

B Wichmann ◽

...

Keyword(s):

Gene Expression ◽

Epithelial Cells ◽

Colorectal Adenoma ◽

Colonic Epithelial Cells ◽

Septin 9

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Penta-O-galloyl-β-d-glucose inhibits phorbol myristate acetate-induced intereukin-8 gene expression in human monocytic U937 cells through its inactivation of nuclear factor-κB

International Immunopharmacology ◽

10.1016/j.intimp.2003.10.010 ◽

2004 ◽

Vol 4 (3) ◽

pp. 377-386 ◽

Cited By ~ 35

Author(s):

G.S. Oh ◽

H.O. Pae ◽

B.M. Choi ◽

H.S. Lee ◽

I.K. Kim ◽

...

Keyword(s):

Gene Expression ◽

Phorbol Myristate Acetate ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

U937 Cells ◽

Myristate Acetate

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Immunoglobulin light chains activate nuclear factor-κB in renal epithelial cells through a Src-dependent mechanism

Blood ◽

10.1182/blood-2010-08-302505 ◽

2011 ◽

Vol 117 (4) ◽

pp. 1301-1307 ◽

Cited By ~ 45

Author(s):

Wei-Zhong Ying ◽

Pei-Xuan Wang ◽

Kristal J. Aaron ◽

Kolitha Basnayake ◽

Paul W. Sanders

Keyword(s):

Epithelial Cells ◽

Tyrosine Phosphorylation ◽

Renal Injury ◽

Src Kinase ◽

Nuclear Factor Κb ◽

Light Chains ◽

Nuclear Factor ◽

Monocyte Chemoattractant Protein 1 ◽

Renal Epithelial Cells ◽

Iκb Kinase

Abstract One of the major attendant complications of multiple myeloma is renal injury, which contributes significantly to morbidity and mortality in this disease. Monoclonal immunoglobulin free light chains (FLCs) are usually directly involved, and tubulointerstitial renal injury and fibrosis are prominent histologic features observed in myeloma. The present study examined the role of monoclonal FLCs in altering the nuclear factor κ light chain enhancer of activated B cells (NF-κB) activity of renal epithelial cells. Human proximal tubule epithelial cells exposed to 3 different human monoclonal FLCs demonstrated Src kinase–dependent activation of the NF-κB pathway, which increased production of monocyte chemoattractant protein-1 (MCP-1). Tyrosine phosphorylation of inhibitor of κB kinases (IKKs) IKKα and IKKβ and a concomitant increase in inhibitor of κB (IκB) kinase activity in cell lysates were observed. Time-dependent, Src kinase–dependent increases in serine and tyrosine phosphorylation of IκBα and NF-κB activity were also demonstrated. Proteasome inhibition partially blocked FLC-induced MCP-1 production. These findings fit into a paradigm characterized by FLC-induced redox-signaling events that activated the canonical and atypical (IKK-independent) NF-κB pathways to promote a proinflammatory, profibrotic renal environment.

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