Cardiac fibroblasts participate in the inflammatory process of heart diseases as sentinel cells of the cardiac tissue. In this study, we investigated the effect of the proinflammatory cytokine, interleukin 1β (IL-1β), on the expression of interleukin 8 (IL-8), which contributes to the induction of innate immunity via the activation and recruitment of innate immune cells, such as neutrophils, to the site of inflammation in canine cardiac fibroblasts. IL-1β mediates IL-8 mRNA expression and protein release in a dose- and time-dependent manner. The IL-β-mediated IL-8 protein release and mRNA expression were inhibited by 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide, an inhibitor of the transcription factor, nuclear factor (NF)-κB. In cells treated with IL-1β, NF-κB p65 and p105 were transiently phosphorylated, indicating the activation of NF-κB. However, IL-1β failed to induce IL-8 mRNA expression in the cells transfected with p65 small interfering RNA (siRNA), but not in those transfected with p105 siRNA. These observations suggest that IL-1β induces IL-8 expression via the activation of NF-κB p65 in canine cardiac fibroblasts.

Situational syncope, which includes rectally mediated reflexes, is defined as syncope induced by a specific situation. Its pathogenesis generally involves disorders of the autonomic nervous system. However, the mechanisms and preventive strategies are not yet well understood. Therefore, we hypothesized that a tachykinin neurokinin-1 receptor might be involved in the autonomic nervous system, and that a neurokinin-1 receptor antagonist could mitigate reflex syncope. This study used a rat model in which the reflex was induced by afferent vagal stimulation with colorectal distension (CRD). In the study, the rats were divided into three groups: non-CRD, CRD, and CRD with a neurokinin-1 receptor antagonist. First, we examined the effect of fosaprepitant, a neurokinin-1 receptor antagonist, on the circulatory response in this model. We then determined the brain regions that showed increased numbers of c-Fos immunoreactive cells in the respective groups. Our results suggest that the colorectal distension procedure reduced blood pressure and that fosaprepitant lowered this response. In addition, the number of c-Fos immunoreactive cells was increased in the caudal ventrolateral medullary region with colorectal distension, and this number was decreased by the administration of fosaprepitant. In conclusion, fosaprepitant might be involved in the vagal reflex pathway and potentially suppress the circulatory response to colorectal distension.