CRC internal access
Hemorrhagic shock (HS) leads to hypoxia-induced systemic inflammation, which can cause acute lung injury (ALI). ALI, a frequent complication of trauma, is aggravated by lung co-morbidities like chronic obstructive pulmonary disease (COPD). COPD is characterized by both pulmonary and systemic hyper-inflammation, and the most common cause for COPD is cigarette smoke (CS) exposure. Anti-inflammatory acting glucocorticoids (GCs) mediate their effects through the glucocorticoid receptor (GR) and are used to treat patients with COPD, whereas their clinical use in ALI remains controversial. Thus insights of the relevance of GR dimerization in mediating lung function in a mouse model of HS and COPD-induced lung injury are of clinical importance and have not been studied yet. In addition, the project aims to investigate if the inflammation during HS and COPD-induced lung injury is dependent on the GR dimerization in macrophages. Moreover the therapeutic activity of GCs is caused by alternative macrophages and requires synergistic gene induction by inflammatory and anti-inflammatory acting signaling pathways to regulate Sphk1 and other markers of alternative macrophage activation. This will be investigated in the model of HS and COPS-induced lung injury.