Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Av. Brasil, No. 4365, Manguinhos, 21045-900, Rio de Janeiro, Brazil.
Laboratório de Neuroquímica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, No. 373; Cidade Universitária, Ilha do Fundão, 21941-902, Rio de Janeiro, Brazil.
Endocrine. 2019 Apr;64(1):169-175. doi: 10.1007/s12020-019-01849-5. Epub 2019 Feb 7.
Glucocorticoid release by adrenals has been described as significant to survive sepsis. The activation of transient receptor potential vanilloid type 1 (TRPV1) inhibited ACTH-induced glucocorticoid release by adrenal glands in vitro.
The aim of this study was to investigate if capsaicin, an activator of TRPV1, would prevent LPS-induced glucocorticoid production by adrenals.
Male Swiss-Webster mice were treated with capsaicin intraperitoneally (0.2 or 2 mg/kg) 30 min before LPS injection. All analyses were performed 2 h after the LPS stimulation, including plasma corticosterone and peritoneal IL-1β and TNF-α levels. Furthermore, murine adrenocortical Y1 cells were used to assess the effects of capsaicin on LPS-induced corticosterone production in vitro.
Capsaicin (2 mg/kg, i.p.) significantly reduced plasma corticosterone levels and adrenal hypertrophy induced by LPS without alter the levels of pro-steroidogenic cytokines IL-1β and TNF-α in peritoneal cavity of mice, while the dose of 0.2 mg/kg of capsaicin did not interfere with adrenal steroidogenesis, attested by RIA and ELISA, respectively. Y1 cells express TRPV1, measured by immunofluorescence and western blot, and capsaicin decreased LPS-induced corticosterone production by these cells in vitro. Capsaicin also induces calcium mobilization in Y1 cells in vitro.
These findings suggest that capsaicin inhibits corticosterone production induced by LPS by acting directly on adrenal cells producing glucocorticoids, in a mechanism probably associated with induction of a cytoplasmic calcium increase in these cells.
肾上腺释放的糖皮质激素被描述为对脓毒症存活至关重要。瞬时受体电位香草酸亚型 1（TRPV1）的激活可抑制体外肾上腺中促肾上腺皮质激素诱导的糖皮质激素释放。
本研究旨在探讨辣椒素（TRPV1 的激活剂）是否会阻止 LPS 诱导的肾上腺糖皮质激素产生。
雄性瑞士-韦伯斯特小鼠在 LPS 注射前 30 分钟腹膜内给予辣椒素（0.2 或 2mg/kg）。所有分析均在 LPS 刺激后 2 小时进行，包括血浆皮质酮和腹腔内 IL-1β 和 TNF-α 水平。此外，还使用鼠肾上腺 Y1 细胞评估辣椒素对体外 LPS 诱导的皮质酮产生的影响。
辣椒素（2mg/kg，ip）显著降低了 LPS 诱导的血浆皮质酮水平和肾上腺肥大，而不改变腹腔中促类固醇生成细胞因子 IL-1β 和 TNF-α 的水平，而 0.2mg/kg 的辣椒素剂量不干扰肾上腺类固醇生成，分别通过 RIA 和 ELISA 证实。Y1 细胞通过免疫荧光和 Western blot 测量表达 TRPV1，辣椒素可减少体外这些细胞中 LPS 诱导的皮质酮产生。辣椒素还可诱导 Y1 细胞体外的钙动员。
这些发现表明，辣椒素通过直接作用于产生糖皮质激素的肾上腺细胞抑制 LPS 诱导的皮质酮产生，其机制可能与这些细胞中细胞质钙增加的诱导有关。
