Mechanism of bronchoprotective effects of a novel natriuretic hormone peptide

Gary Hellermann, Xiaoyuan Kong, Jóhanna Gunnarsdóttir, Homero San Juan, Raji Singam, Sumita Behera, Weidong Zhang, Richard F. Lockey, Shyam S. Mohapatra

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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, pNHP73-102, 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 pNHP73-102 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 NFKB 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 pNHP73-102 -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 pNHP73-102, but not pVAX control, in phorbol myristate acetate-activated A549 cells resulted in a significant decrease in expression of a cotransfected nuclear factorκB (NFκB)-luciferase reporter. Similarly, pNHP73-102 decreased TNF-α-induced NFκB activation in NHBE cells. Furthermore, NHP73-102 but not atrial natriuretic peptide decreased phosphorylation of Erk-1, 2 in A549 cells. Conclusions: Overexpression of pNHP73-102 in epithelial cells causes increased production of intracellular Ca++ and NO, with a concomitant decrease in activation of NFκB and ERK1, 2. These results suggest a bronchodilatory and anti-inflammatory activity of this peptide.

Original languageEnglish
Pages (from-to)79-85
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume113
Issue number1
DOIs
Publication statusPublished - Jan 2004

Bibliographical note

Funding Information:
Supported by the funds by a VA Merit Review Award to SSM and by the Joy McCann Culverhouse Endowment to the University of South Florida Division of Allergy and Immunology Airway Disease Research Center. HS is a recipient of the Fulbright Scholarship.

Other keywords

  • ANP
  • Anti-inflammatory
  • Asthma
  • Bronchodilation
  • ERK
  • Natriuretic
  • NFκB
  • Signaling

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