Cell lines

The human umbilical cord vein cell line EA.hy.926

Preparation Method

DHA at 0.1, 1 and 10µM, hydrocortisone at 0.5µg/mL or vehicle control. After 24h incubation with the pre-treatment, cells were challenged with recombinant human TNFα (50ng/ml) and IL-1β (10ng/mL).

Reaction Conditions

0.5µg/mL for 24 hours

Applications

In the same inflammatory conditions, pre-treatment with hydrocortisone induced a return to baseline, whereas DHA induced an increase of DHA-derived oxylipins that remains subtle at 0,1 and 1 µM, to reach more than half of the total oxylipin output at 10 µM.

Animal models

C57BL/6 mice

Preparation Method

In the hydrocortisone group, mice were subcutaneously injected with 1.5 mg/kg hydrocortisone at 1 h after sepsis induction.

Dosage form

Subcutaneously injection, 1.5 mg/kg

Applications

Model mice were treated with hydrocortisone at 1 h after sepsis induction. After 12 h, the kidney tissue and blood samples were collected. After CLP, the kidney function biomarkers SCR and BUN were significantly elevated in the blood sample of mice, but this elevation was blocked by hydrocortisone treatment.

Hydrocortisone, a natural glucocorticoid secreted by adrenal and extra-adrenal tissues, locally governs the transcription of genes involved in inflammation, immune response, metabolism, and energy homeostasis via binding to its cognate glucocorticoid receptor (GR)^[1]. Glucocorticoids as hydrocortisone and methylprednisolone are known as ABCB1 substrates^[2].

Hydrocortisone was observed to significantly decrease co-culture-induced pp38 MAPK expression in bothpancreatic acinar cells (PACs) and stellate cells (PSCs). The 10 nM concentration of hydrocortisone used in the study was significantly lower than the lowest normal serum cortisol level of approximately 140 nM in human sera^[3].

The Hydrocortisone treatment alleviates sepsis-induced acute kidney injury in mice through HSF-1-mediated transcriptional suppression of XPO1^[4]. Hydrocortisone (70, 140 or 200 mg/kg) treated mice with i.p. injection of did not change either number or percentage of bone marrow B cell subsets. After 24 h of a single i.p. injection of 140 mg/kg of hydrocortisone a reduction in thymus weight and number of thymocytes could be observed. When mice were i.p. injected with hydrocortisone for three consecutive days, there was a depletion of the percentage and number of progenitors and lymphocytes^[2].

References:
[1]. Sridharan, K., Rathore, B., Yousuf, M., Reddy Rachamalla, H. K., Jinka, S., Jaggarapu, M. M. C. S., & Banerjee, R. (2021). Self-assembling derivative of hydrocortisone as glucocorticoid receptor-targeted nanotherapeutics for synergistic, combination therapy against colorectal tumor. Molecular Pharmaceutics, 18(3), 1208- 1228.
[2]. Costa K.M.D, Valente R.C, Silva J.M.C.D, Paiva L.S, Rumjanek V.M, Glucocorticoid susceptibility and in vivo ABCB1 activity differ in murine B cell subsets. An. Acad. Bras. Cienc. 2018; 90 (30304236): 3081-3097. 10.1590/0001-3765201820180364
[3]. BlÄuer, M.; Sand, J.; Laukkarinen, J. Regulation of p38 MAPK and glucocorticoid receptor activation by hydrocortisone in mono-and co-cultured pancreatic acinar and stellate cells. Pancreatology 2021, 21, 384-389.
[4]. L Jin, W Liao, X Zhou, Y Wang, J Qian, et al. Hydrocortisone alleviates sepsis-induced acute kidney injury through HSF-1-mediated transcriptional suppression of XPO1. Tissue and Cell. 2022. 79. doi.org/10.1016/j.tice.2022.101915.