An inhibitory effect of tumor necrosis factor-alpha antagonist to gene expression in monocrotaline-induced pulmonary hypertensive rats model.
10.3345/kjp.2013.56.3.116
- Author:
Jung Hyun KWON
1
;
Kwan Chang KIM
;
Min Sun CHO
;
Hae Soon KIM
;
Sejung SOHN
;
Young Mi HONG
Author Information
1. Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea. ymhong@ewha.ac.kr
- Publication Type:Original Article
- Keywords:
Pulmonary hypertension;
Monocrotaline;
Gene expression;
Infliximab
- MeSH:
Animals;
Antibodies, Monoclonal;
Arteries;
Arterioles;
Endothelin-1;
Gene Expression;
Humans;
Hypertension, Pulmonary;
Injections, Subcutaneous;
Male;
Monocrotaline;
Nitric Oxide Synthase Type III;
Rats;
Rats, Sprague-Dawley;
Receptors, Endothelin;
Tumor Necrosis Factor-alpha;
Infliximab
- From:Korean Journal of Pediatrics
2013;56(3):116-124
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Tumor necrosis factor (TNF)-alpha is thought to contribute to pulmonary hypertension. We aimed to investigate the effect of infliximab (TNF-alpha antagonist) treatment on pathologic findings and gene expression in a monocrotaline-induced pulmonary hypertension rat model. METHODS: Six-week-old male Sprague-Dawley rats were allocated to 3 groups: control (C), single subcutaneous injection of normal saline (0.1 mL/kg); monocrotaline (M), single subcutaneous injection of monocrotaline (60 mg/kg); and monocrotaline + infliximab (M+I), single subcutaneous injection of monocrotaline plus single subcutaneous injection of infliximab (5 mg/kg). The rats were sacrificed after 1, 5, 7, 14, or 28 days. We examined changes in pathology and gene expression levels of TNF-alpha, endothelin-1 (ET-1), endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS), matrix metalloproteinase (MMP)2, and tissue inhibitor of matrix metalloproteinase (TIMP). RESULTS: The increase in medial wall thickness of the pulmonary arteriole in the M+I group was significantly lower than that in the M group on day 7 after infliximab treatment (P<0.05). The number of intra-acinar muscular arteries in the M+I group was lower than that in the M group on days 14 and 28 (P<0.05). Expression levels of TNF-alpha, ET-1, ERA, and MMP2 were significantly lower in the M+I group than in the M group on day 5, whereas eNOS and TIMP expressions were late in the M group (day 28). CONCLUSION: Infliximab administration induced early changes in pathological findings and expression levels of TNF-alpha, and MMP2 in a monocrotaline-induced pulmonary hypertension rat model.
