Tumor necrosis factor-alpha inhibits aquaporin 5 expression in mouse lung epithelial cells.

Abstract

Aquaporin 5 (AQP5), the major water channel expressed in alveolar, tracheal, and upper bronchial epithelium, is significantly down-regulated during pulmonary inflammation and edema. The mechanisms that underlie this decrease in AQP5 levels are therefore of considerable interest. Here we show that AQP5 expression in cultured lung epithelial cells is decreased 2-fold at the mRNA level and 10-fold at the protein level by the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha). Treatment of murine lung epithelial cells (MLE-12) with TNF-alpha results in a concentration- and time-dependent decrease in AQP5 mRNA and protein expression. Activation of the p55 TNF-alpha receptor (TNFR1) with an agonist antibody is sufficient to cause decreased AQP5 expression, demonstrating that the TNF-alpha effect is mediated through TNFR1. Inhibition of nuclear factor kappaB (NF-kappaB) translocation to the nucleus blocks the effect of TNF-alpha on AQP5 expression, indicating that activation of NF-kappaB is required, whereas inhibition of extracellular signal-regulated or p38 mitogen-activated protein kinases showed no effect. These data show that TNF-alpha decreases AQP5 mRNA and protein expression and that the molecular pathway for this effect involves TNFR1 and activated NF-kappaB. The ability of inflammatory cytokines to decrease aquaporin expression may help explain the connection between inflammation and edema.

• Authors: J E Towne, C M Krane, C J Bachurski, A G Menon
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 276 Issue 22 Pg. 18657-64 (Jun 01 2001) ISSN: 0021-9258 [Print] United States
• PMID: 11279049 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• AQP5 protein, human
• Antigens, CD
• Aqp5 protein, mouse
• Aquaporin 5
• Aquaporins
• Membrane Proteins
• NF-kappa B
• RNA, Messenger
• Receptors, Tumor Necrosis Factor
• Receptors, Tumor Necrosis Factor, Type I
• Tumor Necrosis Factor-alpha
• Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Antigens, CD (metabolism)
• Aquaporin 5
• Aquaporins (antagonists & inhibitors, biosynthesis)
• Blotting, Northern
• Blotting, Western
• Cell Line
• Cell Nucleus (metabolism)
• Cell Survival
• Cells, Cultured
• Dose-Response Relationship, Drug
• Edema (metabolism)
• Epithelial Cells (metabolism)
• Humans
• Inflammation (metabolism)
• Lung (metabolism)
• Membrane Proteins
• Mice
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• RNA, Messenger (metabolism)
• Receptors, Tumor Necrosis Factor (metabolism)
• Receptors, Tumor Necrosis Factor, Type I
• Signal Transduction
• Time Factors
• Tumor Necrosis Factor-alpha (metabolism)
• p38 Mitogen-Activated Protein Kinases