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Hypoxia‐Inducible Factor (HIF)‐1 Alpha Expression Induced by Proinflammatory Cytokines in NG108‐15 Neuronal Cells
Author(s) -
Haibara Andrea S,
Sharma Neeru M,
Patel Kaushik P
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1234.3
Subject(s) - proinflammatory cytokine , tumor necrosis factor alpha , endocrinology , medicine , western blot , downregulation and upregulation , chemistry , hypoxia (environmental) , interleukin , transcription factor , biology , cytokine , inflammation , gene , biochemistry , organic chemistry , oxygen
Previous studies have shown that upregulation of proinflammatory cytokines, such as interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α, in the paraventricular nucleus (PVN) has been related to the increased sympathetic outflow seen in heart failure. Recently, we have observed that HIF‐1α, a transcription factor responsible for inducing various genes, is also increased in the PVN of rats with heart failure. In addition, HIF‐1α siRNA administered to the PVN normalizes the increased renal sympathetic nerve activity in rats with HF. However, the specific relationship between proinflammatory cytokines and HIF‐1α expression remains unclear. Therefore, we hypothesized that the increased proinflammatory cytokines would cause augmentation of the HIF‐1α expression. To test this hypothesis, we stimulated NG108‐15 neuronal cell culture with IL‐1β and TNF‐α (10 ng/ml) and evaluated the HIF‐1α protein expression using the Western Blot technique at different time points (4, 8, 16 and 24h). Our results showed a significant increase (1.7 fold) in the expression of HIF‐1α 24h after the treatment of the cells with IL‐1β in comparison with untreated cells. Concomitantly, IL‐1β treatment also induced significant increase in nNOS expression (2.2 fold). In contrast, the treatment of the cells with TNF‐α failed to induce any significant changes in HIF‐1α over this time frame, but induced a significant increase (1.5 fold) in the nNOS expression 16h after treatment. Taken together, these results show that cytokines, particularly IL‐1β, induces enhanced expression of HIF‐1α in NG108‐15 cultured neurons and also suggest that perhaps increased expression of HIF‐1α due to the proinflammatory cytokines is may not be directly involved in the up‐regulation of nNOS in cultured NG108‐15 cells. Support or Funding Information CNPq‐Brazil 234520/2014‐0 and NIH grants HL124104 & HL62222