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Role of hypoxia‐inducible factor‐1α expression in regulatory T cells on nasal polypogenesis
Author(s) -
Jin Jun,
Chang DongYeop,
Kim Sung Ha,
Rha KiSang,
Mo JiHun,
Shin EuiCheol,
Kim Yong Min
Publication year - 2014
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.24472
Subject(s) - rar related orphan receptor gamma , foxp3 , hypoxia inducible factors , flow cytometry , nasal polyps , peripheral blood mononuclear cell , orphan receptor , immunology , biology , andrology , medicine , transcription factor , immune system , gene , biochemistry , in vitro
Objectives/Hypothesis Hypoxia‐inducible factor‐1α (HIF‐1α) is considered as a key molecule in regulating Th17:regulatory T‐cells (Tregs) balance. The aims of this study were to investigate whether HIF‐1α is associated with the RORγ (RAR‐related orphan receptor gamma) expression of Tregs in nasal polyps and to verify whether Staphylococcus enterotoxin B (SEB) is involved in this process. Study Design Clinical experimental study. Methods Forty patients with chronic rhinosinusitis with nasal polyposis were enrolled and divided into eosinophilic nasal polyps (EPs) and noneosinophilic nasal polyps (NEPs) according to the proportion of eosinophils. Fifteen subjects who were undergoing septoplasty were enrolled as control subjects. Expression of HIF‐1α in the tissue was measured using reverse transcriptase‐polymerase chain reaction (RT‐PCR), Western blot, and flow cytometry. The mRNA expression of RORC (RAR‐related orphan receptor C) and HIF‐1α in Tregs separated from tissues were measured by RT‐PCR. Double immunofluorescent staining for RORC/FOXP3 and HIF‐1α/FOXP3 were conducted on the tissues. Expression of RORC and HIF‐1α in Tregs from peripheral blood mononuclear cells (PBMCs) was measured using flow cytometry after stimulation with SEB. Results Expression of RORC and HIF‐1α in Tregs was significantly higher in EPs and NEPs compared with control mucosa, and there was a significant correlation between RORC and HIF‐1α expression in Tregs. Expression of RORC and HIF‐1α mRNA in Tregs separated from the tissues was also significantly higher in nasal polyps compared with control mucosa. Expression of RORC and HIF‐1α in Tregs were increased after 24‐hour stimulation with SEB in the PBMCs. Conclusions HIF‐1α–induced RORC expression in Tregs may play a key role in the pathogenesis of nasal polyps. Level of Evidence NA Laryngoscope , 124:E151–E159, 2014