期刊论文详细信息
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 卷:113
Mechanism of bronchoprotective effects of a novel natriuretic hormone peptide
Article
Hellermann, G ; Kong, XY ; Gunnarsdóttir, J ; San Juan, H ; Singam, R ; Behera, S ; Zhang, WD ; Lockey, RF ; Mohapatra, SS
关键词: ANP;    asthma;    NF kappa B;    ERK;    anti-inflammatory;    bronchodilation;    natriuretic;    signaling;   
DOI  :  10.1016/j.jaci.2003.10.009
来源: Elsevier
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【 摘 要 】

Background: The natriuretic hormone peptide (NHP) (99-126), a C-terminal peptide of pro-atrial natrituretic 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 11 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 factorkappabeta (NFkappaB)-luciferase reporter. Similarly, pNHP(73-102) decreased TNF-alpha-induced NFkappaB activation in NHBE cells. Furthermore, NHP73-102 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.

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