{'fraction_non_alphanumeric': 0.03633916554508748, 'fraction_numerical': 0.029609690444145357, 'mean_word_length': 5.4094827586206895, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Stimulation of Endothelin B Receptor Modulates the Inflammatory Activation of Rat Astrocytes

Abstract: Inside the brain tissue, endothelins play numerous important biological roles. One of the targets, astrocytes, predominantly display endothelin receptor subtype B (ETB). On cultured primary rat astroglial cells, we analyzed the effect of IRL 1620, a selective ETB receptor agonist, on the production of nitric oxide (NO) and the synthesis of interleukin (IL)‐6 and tumor necrosis factor (TNF)‐α. We performed these experiments in the presence or absence of interferon‐γ (IFN‐γ) and/or lipopolysaccharide (LPS). IRL 1620 decreases NO production under basal conditions and after IFN‐γ stimulation. However, during LPS‐induced NO production, IRL 1620 enhances this release. The basal IL‐6 secretion and especially the LPS‐induced synthesis are enhanced by the IRL 1620 stimulation. The LPS‐dependent TNF‐α production is increased by the ETB stimulation. The IRL 1620‐induced decrease of basal NO production is not dependent on Ca2+ entry or on phospholipase C (PLC) activation, as shown by the use of LaCl3 and U73122, respectively. In the presence of LPS, the IRL 1620 potentiation of NO production is inhibited by LaCl3 and U73122. The IRL 1620‐induced increase of IL‐6 is dependent on PLC activation. These results suggest that endothelins can have dual effects depending on the costimulatory factors present. Endothelins thus have important immunomodulatory functions in the brain.