Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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We have demonstrated that 100% oxygen inhalation is beneficial to zymosan-induced generalized inflammation, and reactive oxygen species may be involved in the protection of oxygen treatment. Other investigators suggest that reactive oxygen species may modulate the sympathetic nervous system activity and β2-adrenergic receptor (β2AR)-mediated pathway. Moreover, studies have demonstrated that β2AR agonists are beneficial to sepsis. ⋯ We also showed that zymosan induced the increase in serum 3'-5'-cyclic adenosine monophosphate (cAMP) and the decrease in tissue cAMP. However, oxygen treatment increased the cAMP levels in both serum and tissue, which were partly abolished by pretreatment with butoxamine. Thus, 100% oxygen inhalation may protect against zymosan-induced generalized inflammation in mice partly through activation of β2AR pathway and subsequently enhance cAMP levels in both serum and tissue.
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In the past decades, increased concentrations of the signaling molecule adenosine have been shown to play an important role in the prevention of tissue damage evoked by several stressful circumstances. During systemic inflammation, the circulating adenosine concentration increases rapidly, even up to 10-fold in septic shock patients. ⋯ Importantly, correct interpretation of the effects of adenosine is highly related to the model of inflammation used, e.g., administration of endotoxin or live bacteria. This review will discuss the potential role for adenosine as an immunomodulating and cytoprotective signaling molecule and will discuss its potential role in the treatment of the patient suffering from sepsis.
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High mobility group box 1 (HMGB1), a delayed mediator of proinflammatory cytokines, could initiate and amplify inflammatory responses to infection, injury, and other inflammatory stimuli, and it has emerged as a potential therapeutic target for inflammatory diseases. The overexpression of HMGB1 in endothelial cells has been proved to contribute to the development of these diseases. Because many proinflammatory cytokines expression were suppressed by thiazolidinediones (TZDs), agonists for nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), whether TZDs can inhibit HMGB1 expression and function is of great interest, however, it remains unknown. ⋯ A luciferase reporter assay showed that troglitazone inhibited not only the transcriptional activation of the HMGB1 promoter but also activities of heterologous promoters driven by nuclear factor κB (NF-κB) or activator protein 1 (AP-1) response elements. Altogether, these data suggest that NF-κB and AP-1 may participate in the inhibitory effect on HMGB1 transcription induced by troglitazone. Activation of PPARγ by troglitazone is effective for HMGB1 inhibition via suppressing NF-κB and AP-1 transcriptional activity in endothelial cells, which provides a new potential strategy to suppress excessive HMGB1 in inflammatory diseases.