Contents -- Preface -- Part I MIF Structure and Mechanism of Action -- I-1 MIF, MIF Alleles, and the Regulation of the Host Response Richard Bucala -- 1. Introduction -- 2. MIF Gene -- 3. MIF Production and Signal Transduction -- 4. Innate Immunity -- 5. Adaptive Immunity -- 6. MIF Integrates Immune, Metabolic, and Oncogenic Responses -- 7. MIF Alleles in Human Disease -- 8. Therapeutic Implications and Future Directions -- Acknowledgments -- References -- I-2 MIF and the Chemokine Axis Sandra Kraemer, Christian Weber and Jürgen Bernhagen -- 1. Introduction -- 2. Chemokines: Classes, Structure, Function, and Receptors -- 3. Structural Classification of MIF -- 4. Nonclassical MIF Secretion and Link to Secretion of CLF Chemokines -- 5. Chemokine-like Function (CLF) Chemokines and MIF as a CLF Chemokine -- 6. MIF/ Chemokine Receptor Interactions and Functional Role in Inflammation and Atherogenesis -- 7. Structural Basis Underlying MIF/Chemokine Receptor Interactions -- 8. MIF Receptor Complexes -- 9. Conclusion -- 10. Acknowledgments -- References -- I-3 CD74, the Natural Receptor for MIF, Regulates Cell Survival in Health and Disease Idit Shachar, Maya Gordin, Sivan Cohen, Inbal Binsky, Ayelet Marom and Shirly Becker-Herman -- 1. Introduction -- 2. CD74 (Invariant Chain, Ii) -- 3. CD74 Functions as a Chaperone for MHC Class II -- 4. CD74 as a Signaling Molecule -- 4.1 CD74 is a cell surface receptor that induces signaling cascades -- 4.2 CD74 is subjected to regulated intramembrane proteolysis (RIP) -- 5. MIF Regulates B Cell Survival in a CD74-Dependent Manner -- 5.1 A complex of CD74 and CD44 is essential for initiating the signaling cascade induced by MIF -- 5.2 c-Met and its ligand HGF regulate mature B cell survival in a pathway induced by MIF binding to CD74/CD44.

5.3 MIF induces TAp63 expression, which regulates B cell survival in a CD74-dependent manner -- 6. MIF Is Secreted from Perivascular Bone Marrow Dendritic Cell Clusters that Regulate B Cell Survival -- 7. MIF and CD74 in Tumors -- 7.1 MIF and CD74 in CLL survival -- 7.2 MIF and CD74 regulate CLL homing to the BM -- References -- I-4 Towards the MIF Interactome Jörg Klug and Andreas Meinhardt -- 1. Introduction -- 2. MIF Affects Degradation of Regulatory Proteins by Modulating the Ubiquitin Proteasome System -- 3. Ribosomal Protein S19 as Endogenous Inhibitor of Extracellular MIF -- 4. Interactors Involved in MIF Redox Activity -- 4.1. Insulin -- 4.2. Hepatopoietin (HPO) -- 4.3. Proliferation-associated gene (PAG) protein -- 4.4. p53 -- 4.5. Protein (NM23A) expressed in nonmetastatic cells (NM23-H1) -- 4.6. α1-inhibitor-3 (α1-I3) -- 5 Concluding Remarks -- Acknowledgments -- References -- I-5 Structural Studies of Small Molecule Inhibitors of MIF Yoonsang Cho and Elias J. Lolis -- 1. Introduction -- 2. Small Molecule Structures -- 3. Catalytic Site Inhibitors -- 4. Covalent Inhibitors -- 5. Allosteric and Mixed Inhibitors -- References -- Part II Regulation of MIF Expression -- II-1 Epigenetic Control of MIF Expression Thierry Roger, Jérôme Lugrin, Xavier C. Ding and Thierry Calandra -- 1. Introduction -- 2. Epigenetics -- 2.1 DNA methylation -- 2.2 Post-transcriptional modifications by histone deacetylases -- 3. MIF Gene Structure, Expression and Transcriptional Regulation -- 3.1 MIF gene structure and expression -- 3.2 MIF gene transcriptional regulation -- 4. Epigenetic Control of MIF Expression -- 4.1 The proximal MIF promoter is not methylated -- 4.2 Inhibition of DNA methyl transferases (DNMTs) does not affect MIF gene expression -- 4.3 Inhibition of histone deacetylases (HDACs) impairs MIF gene expression.

4.4 Mechanisms by which HDAC inhibitors inhibit MIF gene expression -- 5. Conclusions -- Acknowledgments -- References -- II-2 Regulation of MIF Gene Expression in the Lung Lili Li and John Baugh -- 1. Introduction -- 2. MIF Gene Structure -- 2.1 Human -- 2.2 Mouse -- 3. Regulation of MIF Expression -- 3.1 Transcription factors involved in MIF gene expression -- 3.1.1 CREB and Sp1 -- 3.1.2 HIF-1 -- 3.1.3 NF-κB -- 3.1.4 Hormone receptors -- 3.1.5 HBP1 -- 3.1.6 AP1 -- 3.2 MIF gene polymorphism -- 4. Summary -- References -- II-3 Hypoxic Adaptation Facilitated by MIF Robert A. Mitchell -- 1. Introduction -- 2. HIF-α Regulation -- 3. MIF, HIF-1α and Tumor-Associated Angiogenesis -- 4. MIF/D-DT-Dependent Angiogenic Growth Factor Expression -- 5. CSN5/JAB-1 and the COP9 Signalosome -- 6. MIF and p53 -- 7. MIF/D-DT Compensation and Therapeutic Implications -- 8. Dopachrome Tautomerases as p53 Antagonists -- References -- Part III Infectious and Inflammatory Diseases -- III-1 MIF in Infectious Diseases Marcelo Torres Bozza and Claudia Neto Paiva -- 1. Introduction -- 2. MIF is a Critical Mediator in Sepsis -- 3. MIF in Extracellular Bacterial Infections -- 4. MIF in Intracellular Bacterial Infections -- 5. MIF in Protozoan Infections -- 5.1. The role of host MIF in the pathogenesis of malaria -- 6. MIF in Viral Infections -- 7. The Role of MIF in Helminth Infections -- 7.1. Host MIF in the pathogenesis in helminth infections -- 8. Future Directions -- References -- III-2 Role of Macrophage Migration Inhibitory Factor (MIF) in Parasitic Diseases Rashmi Tuladhar, Ran Dong, Sanjay Varikuti, John R. David and Abhay R. Satoskar -- 1. Introduction -- 2. MIF and Leishmaniasis -- 2.1 Animal studies -- 2.2 Homologue of MIF in Leishmania -- 3. MIF and Malaria -- 3.1 Animal Studies -- 3.2 MIF in the vasculature -- 3.3 The Placenta and MIF.

3.4 Studies of MIF in malaria in Africa -- 3.5 Studies of MIF malaria in India and Brazil -- 3.6 Plasmodium homologues of MIF -- 4. MIF and Toxoplasmosis -- 4.1 Immunity to toxoplasmosis -- 4.2 Animal studies -- 5. MIF and Schistosomiasis -- 6. MIF and Taeniasis -- 7. MIF and Trypanosomiasis -- 8. MIF and Neospora Infection -- 9. MIF Homologs in Some Other Parasites -- 9.1 Trichinella MIF homolog -- 9.2 Ancytostoma ceylanicum MiF (AceMIF) homolog -- References -- III-3 MIF and Pulmonary Disease Gordon Cooke, Michelle E. Armstrong, Helen Conroy and Seamas C. Donnelly -- 1. Introduction -- 2. MIF and Acute Pulmonary Inflammatory Disease -- 3. Systemic Sepsis and the Lung -- 4. MIF and Chronic Pulmonary Inflammatory Disease -- 4.1 Asthma -- 4.2 Cystic fibrosis -- 4.3 MIF and lung cancer -- 5. Conclusion -- Acknowledgment -- References -- III-4 The Role of MIF in Neurogenic Inflammation Pedro L. Vera and Katherine L. Meyer-Siegler -- 1. Introduction -- 2. Neurogenic Inflammation: Description and Overview -- 3. MIF in the Bladder -- 4. Substance P Induces MIF Release -- 4.1 Substance P induces urothelial MIF release and upregulation in vivo -- 4.2 Substance P induces MIF release from macrophages in vitro -- 5. Substance P-Induced Bladder MIF Release and Upregulation are Mediated by Peripheral Nerve Activation -- 6. MIF Mediates Inflammatory Changes due to Neurogenic Inflammation in the Bladder -- 7. Model of MIF's Role in Neurogenic Inflammation in the Bladder -- 8. Conclusions -- Acknowledgments -- References -- III-5 MIF and Lower Urinary Tract Disorders Anthony DeAngelis, Phillip P. Smith and George A. Kuchel -- 1. Introduction -- 2. Lower Urinary Tract Structure and Function -- 3. MIF Biology in the Lower Urinary Tract -- 3.1 Cellular sites of MIF expression -- 3.2 Regulation of MIF release -- 3.3 Regulation of MIF synthesis.

3.4 Localization of MIF receptors -- 3.5 Urinary tract infections and MIF-protein complexes -- 3.6 Cellular effects of MIF -- 3.6.1 Inflammation -- 3.6.2 Fibroblast survival and fibrosis -- 3.6.3 Smooth muscle cell survival -- 3.6.4 Nerve cell survival -- 4. Potential Roles of MIF in Diagnosis and Management -- 4.1 Urinary tract infection -- 4.2 Bladder outlet obstruction and detrusor underactivity -- 4.3 Bladder cancer -- References -- Part IV Neoplasia -- IV-1 MIF in the Pathogenesis of Urological Cancer Katherine L. Meyer-Siegler and Pedro L. Vera -- 1. Introduction -- 2. MIF as a Marker of Urological Cancer -- 2.1 Increased MIF mRNA and protein in urological tumors -- 2.2 Serum MIF as a urological cancer biomarker -- 2.3 MIF promoter polymorphisms as a marker of urological cancer -- 3. MIF Inactivation via Binding to Endogenous Molecules -- 4. MIF Production and Activity in Cultured Cells: Implications for Prostate and Bladder Cancer -- 5. Conclusions and Outlook -- Acknowledgments -- References -- IV-2 MIF in Ovarian Cancer: Detection and Treatment Guy Nadel, Ayesha B. Alvero and Gil Mor -- 1. Introduction -- 2. Inflammation and Cancer -- 3. Ovarian Cancer and MIF -- 3.1 Detection -- 3.2 Treatment -- 4. Conclusion -- Acknowledgment -- References -- IV-3 The Role of MIF on Tumorigenicity of Embryonic Stem Cells Yi Ren -- 1. Introduction -- 2. Risks of Teratoma Formation after ESC Transplantation -- 3. The Role of MIF in Teratoma Formation -- 3.1 The role of MIF in ESC-induced macrophage activation and infiltration -- 3.2 The role of MIF in ESC-induced angiogenesis -- 4. Strategies for Inhibiting Teratoma Development -- 4.1 Targeting ESCs -- 4.2 Targeting MIF -- 5. Conclusion -- References -- Part V Atherogenesis and Cardiovascular Disease -- V-1 MIF in Atherosclerosis Heidi Noels, Jürgen Bernhagen and Christian Weber -- 1. Introduction.

2. Structural and Functional Classification of MIF.