The role of Syk/IĸB-α/NF-ĸB pathway activation in the reversal effect of BAY 61-3606, a selective Syk inhibitor, on hypotension and inflammation in a rat model of zymosan-induced non-septic shock
| Autor: | Meltem Kacan, Lulufer Tamer-Gumus, Demet Sinem Guden, Bahar Tunctan, Seyhan Sahan-Firat, Meryem Temiz-Resitoglu, Ayse Nihal Sari, Belma Korkmaz, Kafait U. Malik, Hatice Yildirim-Yaroglu, Cuneyt Kemal Buharalioglu, Demet Unsal |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Niacinamide medicine.medical_specialty Physiology Syk Inflammation Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Physiology (medical) Internal medicine medicine Animals Syk Kinase Rats Wistar Pharmacology biology business.industry Nitrotyrosine Zymosan NF-kappa B Shock I-kappa B Kinase Rats Nitric oxide synthase 030104 developmental biology Endocrinology Pyrimidines chemistry Gene Expression Regulation 030220 oncology & carcinogenesis Myeloperoxidase biology.protein medicine.symptom business Tyrosine kinase |
| Zdroj: | Clinical and experimental pharmacologyphysiology. 45(2) |
| ISSN: | 1440-1681 |
| Popis: | Summary Spleen tyrosine kinase (Syk), a non-receptor tyrosine kinase, plays an important role in allergic diseases and inflammation. Syk triggers several intracellular signalling cascades including Toll-like receptor signalling to activate inflammatory responses following fungal infection but the role of this enzyme in zymosan (ZYM)-induced non-septic shock and its impacts on hypotension and inflammation in rats is not well understood. This study was conducted to determine the effects of Syk inhibition on ZYM-induced alterations in the expression and/or activities of Syk, inhibitor ĸB (IĸB)-α, and nuclear factor-ĸB (NF-ĸB) p65. We also examined the effect of Syk inhibition on inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumour necrosis factor (TNF)-α, and activity of myeloperoxidase (MPO) that contributes to hypotension and inflammation. Administration of ZYM (500 mg/kg, i.p.) to male Wistar rats decreased blood pressure and increased heart rate. These changes were associated with increased expression and/or activities of Syk, NF-κB p65, iNOS and COX-2 and decreased expression of IκB-α with enhanced levels of nitrite, nitrotyrosine, 6-keto-PGF1α, and TNF-α and activity of MPO in renal, cardiac and vascular tissues. ZYM administration also elevated serum and tissue nitrite levels. The selective Syk inhibitor BAY 61-3606 (3 mg/kg, i.p) given 1 h after ZYM injection reversed all of these changes induced by ZYM. These results suggest that Syk/IĸB-α/NF-ĸB pathway activation contributes to hypotension and inflammation caused by the production of vasodilator and proinflammatory mediators in the zymosan-induced non-septic shock model. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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