MIF family proteins in lung diseases

Chronic obstructive pulmonary disease (COPD) and lung cancer constitute an enormous disease burden in developed countries. Every year, COPD causes more than three million deaths worldwide. Outcomes for lung cancer are the poorest of all tumor types, with a five-year survival of 10-20%. Exploring the contributions of various proteins involved in these diseases will help in better understanding the disease pathogeneses and developing novel treatment strategies. Macrophage migration inhibitory factor (MIF) is a multi-tasking protein that together with close family member called D-dopachrome tautomerase (D-DT, also referred to as MIF-2) are highly expressed in the lung but their functions remain poorly understood. The research presented in this thesis has focused on studying the roles of MIF family proteins in pulmonary diseases, mainly COPD and lung cancer. We investigated if and how D-DT contributes to epithelial repair in COPD, and then compared the effects of MIF and D-DT on the function of lung epithelial progenitor cells in healthy lung tissue and lung tissue from patients with COPD. We also developed a research tool inhibited intracellular MIF expression and used this to further investigate the biological functions of MIF in lung cancer. Overall, studies in this thesis demonstrated that MIF and its homolog D-DT are associated with COPD and lung cancer and these studies showed novel roles of MIF and D-DT in lung epithelial repair