Mechanism of bronchoprotective effects of a novel natriuretic hormone peptide.

Abstract

BACKGROUND:

The natriuretic hormone peptide (NHP)(99-126), a C-terminal peptide of pro-atrial natriuretic factor (proANF), induces bronchodilatory effects in people with asthma. Recently, another plasmid-encoded C-terminal peptide, pNHP(73-102), was shown to induce a long-lasting bronchoprotective effect in a mouse model of allergic asthma.

OBJECTIVE:

This study was carried out to determine the role of lung epithelial cells in the bronchoprotective and anti-inflammatory activity of these peptides.

METHODS:

Human type II alveolar epithelial cells (A549) and normal human bronchial epithelial (NHBE) cells were transfected with pNHP(73-102) to test the effect of this peptide on activation of these cells. After transfection, cells were analyzed for changes in Ca(++) and nitric oxide (NO) levels. Also, activation of NFkappaB and the extracellularly regulated kinase (ERK) 1, 2 signaling pathway was examined by luciferase reporter assay and phosphorylation studies respectively.

RESULTS:

Analysis of intracellular Ca(++) levels in pNHP(73-102) -transfected A549 or NHBE showed that the peptide increases release. This Ca(++) release was accompanied by an increase in the production of NO. Also, overexpression of pNHP(73-102), but not pVAX control, in phorbol myristate acetate-activated A549 cells resulted in a significant decrease in expression of a cotransfected nuclear factorkappaB (NFkappaB)-luciferase reporter. Similarly, pNHP(73-102) decreased TNF-alpha-induced NFkappaB activation in NHBE cells. Furthermore, NHP(73-102) but not atrial natriuretic peptide decreased phosphorylation of Erk-1, 2 in A549 cells.

CONCLUSIONS:

Overexpression of pNHP(73-102) in epithelial cells causes increased production of intracellular Ca(++) and NO, with a concomitant decrease in activation of NFkappaB and ERK1, 2. These results suggest a bronchodilatory and anti-inflammatory activity of this peptide.

• Authors: Gary Hellermann, Xiaoyuan Kong, Jóhanna Gunnarsdóttir, Homero San Juan, Raji Singam, Sumita Behera, Weidong Zhang, Richard F Lockey, Shyam S Mohapatra
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 113 Issue 1 Pg. 79-85 (Jan 2004) ISSN: 0091-6749 [Print] United States
• PMID: 14713911 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• NF-kappa B
• Nitric Oxide
• Atrial Natriuretic Factor
• NOS3 protein, human
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type III
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases
• Calcium

Topics

• Atrial Natriuretic Factor (genetics, physiology)
• Calcium (metabolism)
• Cell Line
• Epithelial Cells (metabolism)
• Humans
• Immunoblotting
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase (metabolism)
• Nitric Oxide Synthase Type III
• Pulmonary Alveoli (cytology)
• Transfection