Interdisciplinary Center for Aquaculture Research (INCAR), Department of Oceanography, Biotechnology Center, University of Concepción, 4030000 Concepción, Chile.
Interdisciplinary Center for Aquaculture Research (INCAR), Department of Oceanography, Biotechnology Center, University of Concepción, 4030000 Concepción, Chile.
Brain Behav Immun. 2018 Jul;71:169-181. doi: 10.1016/j.bbi.2018.03.023. Epub 2018 Mar 21.
A fever, or increased body temperature, is a symptom of inflammation, which is a complex defence reaction of the organism to pathogenic infections. After pathogens enter the body, immune cells secrete a number of agents, the functions of which stimulate the body to develop a functional immune and fever response. In mammals it is known that PGE is the principal mediator of fever. The extent to which PGE and other pro-inflammatory cytokines such as TNF-α, IL-6, or IL-1β could be involved in the induction of behavioural fever in fish remains to be clarified. Several members of the transient receptor potential (TRP) family of ion channels have been implicated as transducers of thermal stimuli, including TRPV1 and TRPV2, which are activated by heat. Here we show that members of the TRP family, TRPV1 and TRPV4, may participate in the coordination of temperature sensing during the behavioural fever. To examine the behavioral fever mechanism in Salmo salar an infection with IPNV, infectious pancreatic necrosis virus, was carried out by an immersion challenge with 10 × 10 PFU/mL of IPNV. Behavioural fever impacted upon the expression levels of both TRPV1 and TRPV4 mRNAs after the viral challenge and revealed a juxtaposed regulation of TRPV channels. Our results suggest that an increase in the mRNA abundance of TRPV1 is tightly correlated with a significant elevation in the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and PGE) in the Pre-Optic Area (POA) and cytokine release in plasma. Together, these data indicate that the reduction of TRPV4 expression during behavioural fever may contribute to the onset of behavioural fever influencing movement toward higher water temperatures. Our data also suggest an effect of TRPV channels in the regulation of behavioural fever through activation of EP3 receptors in the central nervous system by PGE induced by plasma-borne cytokines. These results highlight for first time in mobile ectotherms the key role of pro-inflammatory cytokines and TRPV channels in behavioural fever that likely involves a complex integration of prostaglandin induction, cytokine recognition and temperature sensing.
发热或体温升高是炎症的症状，炎症是机体对病原体感染的复杂防御反应。病原体进入机体后，免疫细胞会分泌多种物质，其功能刺激机体产生功能性免疫和发热反应。在哺乳动物中，PGE 是发热的主要介质。PGE 和其他促炎细胞因子（如 TNF-α、IL-6 或 IL-1β）在鱼类行为性发热中的作用程度仍有待阐明。瞬时受体电位（TRP）家族的一些离子通道成员被认为是热刺激的传感器，包括 TRPV1 和 TRPV2，它们被热激活。在这里，我们表明 TRP 家族成员 TRPV1 和 TRPV4 可能参与了行为性发热过程中的温度感应协调。为了研究鲑鱼的行为性发热机制，我们进行了传染性胰脏坏死病毒（IPNV）感染的实验，通过 10×10 PFU/mL 的 IPNV 浸泡挑战进行。病毒攻击后，行为性发热影响了 TRPV1 和 TRPV4 mRNA 的表达水平，并揭示了 TRPV 通道的并列调节。我们的结果表明，TRPV1 mRNA 丰度的增加与前脑区（POA）中促炎细胞因子（IL-1β、IL-6、TNF-α 和 PGE）表达的显著升高以及血浆中细胞因子的释放密切相关。总之，这些数据表明，行为性发热期间 TRPV4 表达的减少可能有助于行为性发热的发生，影响向更高水温的运动。我们的数据还表明，TRPV 通道通过 PGE 诱导的 EP3 受体在中枢神经系统中的激活，在行为性发热的调节中发挥作用，PGE 由血浆来源的细胞因子诱导。这些结果首次在移动的变温动物中强调了促炎细胞因子和 TRPV 通道在行为性发热中的关键作用，这可能涉及到前列腺素诱导、细胞因子识别和温度感应的复杂整合。
