MIF promotes B cell chemotaxis through the receptors CXCR4 and CD74 and ZAP-70 signaling.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with chemokine-like functions that plays a pivotal role in the pathogenesis of inflammatory diseases by promoting leukocyte recruitment. We showed that MIF promotes the atherogenic recruitment of monocytes and T cells through its receptors CXCR2 and CXCR4. Effects of MIF on B cell recruitment have not been addressed.

Deficiency of endothelial CXCR4 reduces reendothelialization and enhances neointimal hyperplasia after vascular injury in atherosclerosis-prone mice.

Objective: The Cxcl12/Cxcr4 chemokine ligand/receptor axis mediates the mobilization of smooth muscle cell progenitors, driving injury-induced neointimal hyperplasia. This study aimed to investigate the role of endothelial Cxcr4 in neointima formation.

Approach And Results: β-Galactosidase staining using bone marrow x kinase (Bmx)-CreER(T2) reporter mice and double immunofluorescence revealed an efficient and endothelial-specific deletion of Cxcr4 in Bmx-CreER(T2+) compared with Bmx-CreER(T2-) Cxcr4-floxed apolipoprotein E-deficient (Apoe(-/-)) mice (referred to as Cxcr4(EC-KO)ApoE(-/-) and Cxcr4(EC-WT) ApoE(-/-), respectively).

Genetic diversity and distribution of human norovirus in China (1999-2011).

Noroviruses (NoVs) are a leading cause of epidemic and sporadic acute gastroenteritis worldwide. However, the genetic diversity and geographical distribution of NoV isolates from China have not been well described thus far. In this study, all NoV sequences obtained in China from 1999 to 2011 (n = 983), both partial and complete genomes, were downloaded from GenBank.

The role of macrophage migration inhibitory factor in anesthetic-induced myocardial preconditioning.

Introduction: Anesthetic-induced preconditioning (AIP) is known to elicit cardioprotective effects that are mediated at least in part by activation of the kinases AMPK and PKCε as well as by inhibition of JNK. Recent data demonstrated that the pleiotropic cytokine macrophage migration inhibitory factor (MIF) provides cardioprotection through activation and/or inhibition of kinases that are also known to mediate effects of AIP. Therefore, we hypothesized that MIF could play a key role in the AIP response.

Bone marrow-specific knock-in of a non-activatable Ikkα kinase mutant influences haematopoiesis but not atherosclerosis in Apoe-deficient mice.

Background: The Ikkα kinase, a subunit of the NF-κB-activating IKK complex, has emerged as an important regulator of inflammatory gene expression. However, the role of Ikkα-mediated phosphorylation in haematopoiesis and atherogenesis remains unexplored. In this study, we investigated the effect of a bone marrow (BM)-specific activation-resistant Ikkα mutant knock-in on haematopoiesis and atherosclerosis in mice.

Crosstalk between sentinel and helper macrophages permits neutrophil migration into infected uroepithelium.

The phagocytes of the innate immune system, macrophages and neutrophils, contribute to antibacterial defense, but their functional specialization and cooperation is unclear. Here, we report that three distinct phagocyte subsets play highly coordinated roles in bacterial urinary tract infection. Ly6C(-) macrophages acted as tissue-resident sentinels that attracted circulating neutrophils and Ly6C(+) macrophages.

Novel insights into the mechanism of cell-based therapy after chronic myocardial infarction.

Cell transplantation therapy is considered a novel and promising strategy in regenerative medicine. Recent studies point out that paracrine effects and inflammation induced by transplanted cells are key factors for the improvement of myocardial function. The present study aims at differentiating paracrine effects from inflammatory reactions after cell transplantation.

Efficient purification and concentration of viruses from a large body of high turbidity seawater.

Marine viruses are the most abundant entities in the ocean and play crucial roles in the marine ecological system. However, understanding of viral diversity on large scale depends on efficient and reliable viral purification and concentration techniques. Here, we report on developing an efficient method to purify and concentrate viruses from large body of high turbidity seawater.

Platelets are a previously unrecognised source of MIF.

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine with chemokine-like functions and a role in atherogenesis. MIF is secreted by various cells including endothelial cells and macrophages. Platelets are another prominent cell type with a role in atherogenesis and are a rich source of atherogenic chemokines.

Arrest Functions of the MIF Ligand/Receptor Axes in Atherogenesis.

Macrophage migration inhibitory factor (MIF) has been defined as an important chemokine-like function (CLF) chemokine with an essential role in monocyte recruitment and arrest. Adhesion of monocytes to the vessel wall and their transendothelial migration are critical in atherogenesis and many other inflammatory diseases. Chemokines carefully control all steps of the monocyte recruitment process.

Endothelial CSN5 impairs NF-κB activation and monocyte adhesion to endothelial cells and is highly expressed in human atherosclerotic lesions.

The COP9 signalosome (CSN), a multifunctional protein complex involved in the regulation of cullin-RING-E3 ubiquitin ligases (CRLs), has emerged as a regulator of NF-κB signalling. As NF-κB drives the expression of pro-inflammatory and pro-atherosclerotic genes, we probed the yet unknown role of the CSN, in particular CSN5, on NF-κB-mediated atherogenic responses in endothelial cells. Co-immunoprecipitation in human umbilical vein endothelial cells (HUVECs) revealed the presence of a super-complex between IKK and CSN, which dissociates upon TNF-α stimulation.

Hetero-oligomerization of chemokine receptors: diversity and relevance for function.

The G protein-coupled receptor (GPCR) family of membrane receptors encompasses over 1000 members, representing the largest known receptor family, with a variety of structurally different ligands. GPCRs are favorite targets for drug development in numerous diseases. Chemokine receptors are an important GPCR sub-class and are known to play a crucial role in the regulation of multiple physiological and various pathophysiological processes, including inflammation, atherosclerosis, cancer, and viral infections.

The vascular biology of macrophage migration inhibitory factor (MIF). Expression and effects in inflammation, atherogenesis and angiogenesis.

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with chemokine-like functions. MIF is a critical mediator of the host immune and inflammatory response. Dysregulated MIF expression has been demonstrated to contribute to various acute and chronic inflammatory conditions as well as cancer development.

Differential roles of angiogenic chemokines in endothelial progenitor cell-induced angiogenesis.

This study aimed to analyze the role of endothelial progenitor cell (EPC)-derived angiogenic factors and chemokines in the multistep process driving angiogenesis with a focus on the recently discovered macrophage migration inhibitory factor (MIF)/chemokine receptor axis. Primary murine and murine embryonic EPCs (eEPCs) were analyzed for the expression of angiogenic/chemokines and components of the MIF/CXC chemokine receptor axis, focusing on the influence of hypoxic versus normoxic stimulation. Hypoxia induced an upregulation of CXCR2 and CXCR4 but not CD74 on EPCs and triggered the secretion of CXCL12, CXCL1, MIF, and vascular endothelial growth factor (VEGF).

Abdominal aorta as a recipient artery: Using a free latissimus dorsi myocutaneous flap to close hip and pelvic defects.

Introduction: Free tissue transfer (FTT) is now a common procedure in many surgical centres around the world and it has shown well established results especially in the field of reconstructive surgery. The choice of FTT depends on the size of defect, nature of tissue, length of pedicle and donor site morbidity. Notwithstanding, FTT is complex and always depending on a sufficient recipient vessel.

Fibrocytes in Fibrotic Diseases and Wound Healing.

Background: First described in 1994, fibrocytes are now appreciated to participate in different inflammatory and fibrogenic processes as well as in wound healing. Fibrocytes are unique in their expression of both myeloid and connective tissue products, which include a distinct cytokine and surface marker expression profile. Recent studies suggest their clinical utility as predictive biomarkers and as targets for therapeutic intervention.

Role for CD74 and CXCR4 in clathrin-dependent endocytosis of the cytokine MIF.

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that plays a role in innate and adaptive immunity. Depending on the cellular context and disease state, MIF signaling is mediated by its receptors CXCR2, CXCR4 and/or CD74. Although it is known that MIF is endocytosed, the exact mechanism has remained unknown.

MIF-chemokine receptor interactions in atherogenesis are dependent on an N-loop-based 2-site binding mechanism.

Macrophage migration inhibitory factor (MIF) is a cytokine that mediates inflammatory diseases. MIF promotes atherogenic leukocyte recruitment through a promiscuous, yet highly affine, interaction with CXCR2 and CXCR4. Binding to CXCR2 is dependent on a pseudo-(E)LR motif in MIF, but a second interaction site has been elusive.

Activation of the JNK signalling pathway by macrophage migration inhibitory factor (MIF) and dependence on CXCR4 and CD74.

c-Jun N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase (MAPK) family and controls essential processes such as inflammation, cell differentiation, and apoptosis. JNK signalling is triggered by extracellular signals such as cytokines and environmental stresses. Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine with chemokine-like functions in leukocyte recruitment and atherosclerosis.

Regulation of nuclear import and export of negative cofactor 2.

The negative cofactor 2 (NC2) is a protein complex composed of two subunits, NC2alpha and NC2beta, and plays a key role in transcription regulation. Here we investigate whether each subunit contains a nuclear localization signal (NLS) that permits individual crossing of the nuclear membrane or whether nuclear import of NC2alpha and NC2beta depends on heterodimerization. Our results from in vitro binding studies and transfection experiments in cultured cells show that each subunit contains a classical NLS (cNLS) that is recognized by the importin alpha/beta heterodimer.

Histone H1 and its isoforms: contribution to chromatin structure and function.

The lysine-rich H1 histone family in mammals includes eleven different subtypes, and thus it is the most divergent class of histone proteins. The central globular H1 domain asymmetrically interacts with DNA at the exit or entry end of the nucleosomal core DNA, and the C-terminal domain has a major impact on the linker DNA conformation and chromatin condensation. H1 histones are thus involved in the formation of higher order chromatin structures, and they modulate the accessibility of regulatory proteins, chromatin remodeling factors and histone modification enzymes to their target sites.

H1 histone subtype constitution and phosphorylation state of the ageing cell system of human peripheral blood lymphocytes.

Until a few years ago, the H1 histones were exclusively considered to be the architectural proteins of chromatin involved in chromatin condensation. However there is now increasing data to support the hypothesis that the H1 subtypes are involved in genomic integrity and that they may have unexpected functional roles in various biological processes such as in differentiation and DNA repair, apoptosis and lifespan. Moreover, the H1 histones are phosphorylated to a great extent.

Resonant nano-cluster devices.

The resonance-enhanced absorption (REA) by metal clusters on a surface is an effective technique on which to base bio-optical devices. A four-layer device consisting of a metal mirror, a polymer or glass-type distance layer, a biomolecule interaction layer and a sub-monolayer of biorecognitively bound metal nano-clusters is reported. Experiments indicate a strong influence of the resonator homogeneity on the absorption maximum.

Glucagon-stimulated but not isoproterenol-stimulated glucose formation inhibition by interleukin-6 in primary cultured rat hepatocytes.

During prolonged sepsis, impairment of glucose supply by the liver leads to hypoglycemia. Our aim was to investigate whether proinflammatory cytokine interleukin-6, a major mediator of the hepatic acute phase reaction, could contribute to this impairment by inhibiting hepatic glucose production stimulated by glucagon or isoproterenol in rat hepatocytes. Interleukin-6 inhibited the stimulation of glucose formation from glycogen by glucagon but not by isoproterenol in cultured rat hepatocytes.