Maryam Rameshrad; Nasrin Maleki-Dizaji; Haleh Vaez; Hamid Soraya; Ailar Nakhlband; Alireza Garjani
Volume 12, Issue 2 , June 2015, , Pages 104-116
Abstract
Background: Myocardial dysfunction is one of the major complications in patients with sepsis where there is a relationship between the blood level of cytokines and the onset of myocardial depression. In many cases of sepsis, the presence of Lipopolysaccharide (LPS) has been established. LPS Binding Protein ...
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Background: Myocardial dysfunction is one of the major complications in patients with sepsis where there is a relationship between the blood level of cytokines and the onset of myocardial depression. In many cases of sepsis, the presence of Lipopolysaccharide (LPS) has been established. LPS Binding Protein (LBP) bound endotoxin is recognized by CD14/toll-like receptor-4 (TLR4) complexes in innate immune cells which stimulates TNF-α release. Objectives: To investigate whether isolated rat heart is capable of producing TNF-α locally through TLR4 activation by LPS. Methods: Using langendorff method, LPS in 120 mL of the modified KrebsHenseleit buffer solution (KHBS) at final concentration of 1 µg/mL was perfused at recycling mode. The effect of LPS on cardiac function was evaluated. To assess the TLR4 activity and TNF-α release, western blotting, real time-PCR, and ELISA were used. Results: Compared with control, coronary perfusion pressure (CPP) as well as left ventricular developed pressure (LVDP), maximum and minimum rates of the left ventricular developed pressure (dP/dtmax; dP/dtmin; p<0.001) were depressed to a maximum level after 180 minutes recycling with LPS. This myocardial depression was associated with a significant increase in TLR4 expression (p<0.01), MyD88 activity (p<0.01) and TNF-α (p<0.05) concentration in the heart tissue. Conclusion: The results of this study show that heart is capable of producing TNF-α through TLR4 and MyD88 activation independent of classic immune system and suggest a local immune response.
Bahador Bagheri; Bahram Sohrabi; Aliakbar Movassaghpur; Siminozar Mashayekhi; Afagh Garjani; Mehriar Shokri; Mohammad Noori; Alireza Garjani
Volume 9, Issue 3 , September 2012, , Pages 149-158
Abstract
Background: Toll like receptors (TLRs) are well recognized players in inflammatory conditions. Among them TLR-4 is involved in chronic inflammatory processes such as formation of atherosclerotic plaques. Objective: The present study was aimed to examine the effects of percutanoeus coronary intervention ...
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Background: Toll like receptors (TLRs) are well recognized players in inflammatory conditions. Among them TLR-4 is involved in chronic inflammatory processes such as formation of atherosclerotic plaques. Objective: The present study was aimed to examine the effects of percutanoeus coronary intervention (PCI) as a revascularization method on monocyte expression of hTLR-4 and on the serum levels of two proinflammatory cytokines (TNF-α and IL-1β). Methods: Blood samples were obtained from 41 patients with stable angina who were candidates for PCI. The samples were collected immediately before and 2h and 4h after PCI. The expression of hTLR-4 on CD14+ monocytes and the serum levels of TNF-α and IL-1β were measured using flowcytometry and ELISA techniques, respectively. Results: By comparing the frequency of circulating hTLR-4+/CD14+ monocytes at different time points, it was observed that PCI procedure up regulates the monocyte expression of hTLR-4 (p<0.05). The increase in expression was associated with the elevation of the serum levels of proinflammatory cytokines (p<0.05). There was a significant correlation between monocyte expression of hTLR-4 and serum levels of TNF-α and IL-1β only before PCI. In spite of parallel increase in the serum levels of proinflammatory cytokines and the monocyte expression of hTLR-4, the correlation did not attain a significant level after PCI intervals. Conclusion: PCI is positively associated with an increase in the monocyte expression of hTLR-4. It is also associated with the elevation in the serum levels of proinflmmatory cytokines. These findings suggest that hTLR-4 monocyte expression may be used as a potential prognostic tool in patients with stable angina undergoing PCI.