CTRP9 inhibits expressions of IL-6 and TNF-α in pulmonary microvascular endothelial cell under hypoxia condition
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Graphical Abstract
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Abstract
AIM To investigate the effects of CTRP9 on hypoxia-induced expressions of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in pulmonary microvascular endothelial cells (PMVECs). METHODS SD rats were randomly divided into normoxic group and hypoxic group. The rats in the hypoxic group were exposed to low-pressure and low-oxygen condition in an auto-modulating hypobaric and hypoxic cabin (air pressure 55 kPa, oxygen concentration 10%) for 28 days to establish the animal model of hypoxic pulmonary hypertension (HPH). The histopathological change, the hemodynamic index and the right ventricular hypertrophy index of rats were detected. The mRNA levels of IL-6 and TNF-α in lungs were determined by RT-PCR and serum IL-6 and TNF-α were measured by ELISA. Primary PMVEC were cultured under normoxia, hypoxia (50 ml/L O2) or hypoxia with CTPR9 treatment and mRNA of IL-6 and TNF-α in the cell lysate was determined by RT-PCR. RESULTS In the hypoxia group, the right ventricular systolic pressure, the right ventricular hypertrophy index and the thickness of pulmonary arterial wall were increased compared with those in the normoxia group(P<0.05). The expressions of IL-6 and TNF-α in PMVEC increased significantly under hypoxia environment(P<0.05) and CTRP9 treatment effectively inhibited the increase(P<0.05). CONCLUSIONS The expressions of IL-6 and TNF-α increase in HPH rats. CTRP9 could effectively inhibit the expressions and secretions of inflammatory cytokines IL-6 and TNF-α in PMVEC in hypoxia condition, which makes CTRP9 a potential therapy to prevent and limit the development of HPH.
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