Proteomic and genomic analysis of inflammatory resolution in mouse and man

许多慢性衰弱性疾病，包括支气管炎、银屑病关节炎、系统性红斑狼疮和克罗恩病。S疾病以炎症失调为主要驱动力。然而，这些疾病无法解决，并在本质上复发。相比之下，还有其他炎症性疾病，如链球菌引起的肺炎，通常不会造成持久的组织损伤。因此,它吗?我们有理由认为，一些炎症反应是由内源性因素控制的，这些内源性因素表明它们的停止，而另一些炎症反应可能是失调的。这项研究计划背后的想法来自于一个简单的观察，即由手指刺痛或蜜蜂蜇伤引起的急性炎症，从开始（肿胀、疼痛和发红）到结束（肿胀和疼痛减轻，组织恢复到原来的形式，统称为消退）有一个自然的过程。然而，多年来人们一直没有认识到炎症的消退是由受伤组织产生的因素控制的。我们的想法是，我们可以利用这些因素或开发模仿其作用的药物，以迫使慢性炎症疾病解决或关闭。这种方法将允许炎症反应正常进展，并中和有害物质，这是任何炎症反应的基础，但在最小组织损伤的情况下及时解决事件。然而，与已知的驱动炎症的众多信号不同，我们对关闭炎症的预分解因素知之甚少。为了解决这个问题，我们希望应用强大的最先进的技术来识别炎症消退时存在的基因和蛋白质。这个想法是，在决议过程中，这些因素的表达就像？停止开关?对炎症。这个项目的一个独特之处在于，人类样本来源于简单但很容易理解的自限性炎症模型，以补充将在小鼠身上进行的实验。通过使用从人类解决炎症中获得的样本，我们可以与我们的动物研究直接相关，并为本项目的总体目标和数据结果增加更大的力量。这一研究体系背后的总体理念是建立一个与解决相关的可溶性因子和基因信息库，旨在根据其作用模式开发药物，即帮助推动持续/慢性炎症进入促解决途径。

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.