title: Angiotensin II induces interleukin-6 expression in astrocytes: Role of reactive oxygen species and NF-κB.
abstract: Previously, we showed that the bio-peptide angiotensin (Ang) II induces interleukin-6 (IL-6) in cultured astrocytes; however, the mechanism(s) involved in this effect were unknown. In the current study, we determined in brainstem and cerebellum astrocytes from the spontaneously hypertensive rat (SHR), the effect of Ang II to induce IL-6 as well as reactive oxygen species (ROS) generation. Results from this study showed that Ang II significantly induced the differential expression of IL-6 mRNA and protein levels in astrocytes from both regions of Wistar and SHRs. There were differences in the ability of Ang II to induce IL-6 mRNA and protein levels, but these differences were not apparent at all time points examined. Ang II also induced ROS generation, but there were no significant differences between ROS generation in SHR samples as compared to the Wistar samples. Ang II-induced IL-6 levels were mediated via the AT1/Nuclear Factor Kappa beta/ROS pathway. Overall, our findings suggest that there may be dysregulation in IL-6 production from astrocytes, contributing to differences observed in SHRs versus its normotensive control. Elucidating the mechanisms involved in Ang II pro-inflammatory effects in the central nervous system may lead to the development of novel therapeutic strategies that can be harnessed not just to treat hypertension, but other Ang II-mediated diseases as well.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, United States.
authors.forename: Yugandhar V
authors.initials: YV
authors.lastname: Gowrisankar
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, United States. Electronic address: miclark@nova.edu.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Clark
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006835:Hydrazones / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D009593:Nitroimidazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors
chemical_list: D006835:Hydrazones; D007093:Imidazoles; D015850:Interleukin-6; D016328:NF-kappa B; D009593:Nitroimidazoles; D011725:Pyridines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C555826:YCG 063; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan
keywords: Angiotensin II; Astrocytes; Interleukin-6; NF-κB; Reactive oxygen species