Angiotensin II AT1 blockade reduces the lipopolysaccharide-induced innate immune response in rat spleen
| Autor: | Tsuyoshi Nishioku, Enrique Sanchez-Lemus, Juan M. Saavedra, Martina Baliova, Julius Benicky, Ignacio M. Larrayoz, Jin Zhou, Jaroslav Pavel |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Lipopolysaccharides
Male medicine.medical_specialty Angiotensin receptor Physiology CD14 Lipopolysaccharide Receptors Nitric Oxide Synthase Type II Tetrazoles Blood Pressure Inflammation Biology Dinoprostone Receptor Angiotensin Type 1 Immune system Physiology (medical) Internal medicine medicine Animals Rats Wistar Membrane Glycoproteins Angiotensin II receptor type 1 Innate immune system Biphenyl Compounds NF-kappa B NADPH Oxidases Angiotensin II Immunity Innate Rats Blockade Toll-Like Receptor 4 Disease Models Animal Endocrinology Cyclooxygenase 2 NADPH Oxidase 2 Cytokines Benzimidazoles Inflammation Cytokines Neuroimmune Interactions medicine.symptom Reactive Oxygen Species Angiotensin II Type 1 Receptor Blockers hormones hormone substitutes and hormone antagonists Spleen |
| Zdroj: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 296:R1376-R1384 |
| ISSN: | 1522-1490 0363-6119 |
| DOI: | 10.1152/ajpregu.90962.2008 |
| Popis: | ANG II AT1 receptor blockade reduces inflammation in hypertension. To determine whether ANG II AT1 receptor blockers (ARBs) influence the innate immune inflammatory response in normotensive rats, we studied rat plasma and spleen after a 3-day subcutaneous pretreatment with the ARB candesartan followed by a single dose of the bacterial endotoxin LPS (50 μg/kg ip). Peripheral administration of LPS to rodents produced a generalized inflammatory response with increased release of TNF-α, IL-1β, and IL-6 into the circulation. Candesartan pretreatment reduced the LPS-induced release of TNF-α, IL-1β, and IL-6 into the circulation. The red pulp of rat spleen expressed large numbers of AT1 receptors and the LPS receptors Toll-like receptor 4 and CD14. Candesartan administration significantly blocked AT1 receptors. The ARB reduced the LPS-induced upregulation of CD14 gene expression; expression of TNF-α and IL-6 mRNA and protein; expression of IL-1β and IκB-α mRNA; COX-2 mRNA and protein expression and PGE2 concentration; inducible nitric oxide synthase (iNOS) gene and protein expression and iNOS activity; and Nox2 gene expression and 8-isoprostane levels. In addition, candesartan reduced the CD14 protein expression in saline- and LPS-treated rats. Our results suggest that AT1 receptors are essential for the development of the full innate immune response to bacterial endotoxin. The ARB decreased the general peripheral inflammatory reaction to LPS and partially decreased the inflammatory response in the spleen. An unrestricted innate immune response to the bacterial endotoxin may have deleterious effects for the organism and may lead to development of chronic inflammatory disease. We postulate that ARBs may have therapeutic effects on inflammatory conditions. |
| Databáze: | OpenAIRE |
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