Proteomic and genomic analysis of inflammatory resolution in mouse and man

许多慢性衰弱疾病，如支气管炎、银屑病、系统性红斑狼疮、克罗恩？S病等，炎症调节失调是其主要驱动力。然而，这种疾病不能解决，并在性质上复发。相比之下，还有其他炎症性疾病，如链球菌引起的肺炎，通常在不造成持久组织损伤的情况下得到缓解。因此，S有理由认为，一些炎症反应受控于内源性因素，这些内源性因素标志着炎症反应的停止，而另一些炎症反应可能处于失调状态。这项研究建议背后的想法来自一个简单的观察，即例如由手指刺痛或蜜蜂叮咬损伤引起的急性炎症从开始(肿胀、疼痛和发红)到结束(肿胀和疼痛的减少以及组织恢复到以前的形式，统称为消退)有一个自然的过程。然而，多年来，人们一直没有意识到炎症的消退是由受损组织产生的因子控制的。我们的想法是，我们可以利用这些因素或开发模仿它们的作用的药物，以迫使慢性炎症性疾病消退或关闭。这种方法将允许炎症反应正常进行，并中和作为任何炎症反应的基础的损害性因素，但以最小的组织损伤及时解决事件。然而，与已知的推动炎症的众多信号不同，人们对关闭炎症的分解前因子知之甚少。为了解决这个问题，我们希望应用强大的最先进技术来识别炎症消退时存在的基因和蛋白质。其想法是，在解决过程中，这些因素的表达起到了停止开关的作用。治疗炎症。该项目的一个独特方面是从简单但众所周知的自限性炎症模型中提取的人类样本，以补充将在小鼠身上进行的实验。通过使用从人类消炎中获得的样本，我们可以与我们的动物研究直接相关，并为该项目的总体目标和数据结果增加更大的力量。这一研究机构背后的总体哲学是产生一个参与分解的可溶性因子和基因的信息库，目的是根据它们的作用模式开发药物，即帮助推动持续/慢性炎症沿着促进分解的途径前进。

Many chronic debilitating diseases including bronchitis, psoriatic arthritis, systemic lupus erythematosus and Crohn?s disease have dysregulated inflammation as their main driving force. However, such diseases fail to resolve and become recurrent in nature. In contrast, there are other inflammatory diseases such as streptococcal-induced pneumonia, which typically resolve without causing lasting tissue injury. Therefore, it?s reasonable to suggest that some inflammatory responses are under the control of endogenous factors that signal their cessation, which may be dysregulated in others. The idea behind this research proposal comes from the simple observation that acute inflammation elicited, for example, by a finger prick or bee-sting injury has a natural progression from start (swelling, pain and redness) to finish (reduction in swelling and pain and restoration of the tissue to its prior form, collectively called resolution). However, it has remained unappreciated for many years that resolution of inflammation is under the control of factors manufactured by the injured tissue. Our thinking is that we could use these factors or develop drugs that mimic their action in order to force chronic inflammatory diseases into resolving or switching off. This approach would allow the inflammatory response to progress as normal and neutralise the injurious agent, which is the basis of any inflammatory response, but bring about resolution of the event in a timely manner with minimal tissue injury. However, unlike the multitude of signals known to drive inflammation very little is known about the pre-resolution factors that switch it off. In order to address this we wish to apply powerful state-of-the-art technology to identify the genes and proteins that are present as inflammation resolves. The idea being that the expression of such factors during resolution acts as ?stop switches? for inflammation. One of the unique aspects of this project is that of human samples derived from simple but well-understood models of self-limiting inflammation to complement the experiments that will be done in mouse. By using samples obtained from human resolving inflammation we can get a direct correlation with our animal studies and add greater strength to the overall objectives of this project and data outcome. The overall philosophy behind this body of research is to generate an information bank of soluble factors and genes involved in resolution with the intention of developing drugs based on their mode of action i.e. to help drive ongoing/chronic inflammation down a pro-resolution pathway.