Richard Bucala

Bio: Richard Bucala is an academic researcher from Yale University. The author has contributed to research in topics: Macrophage migration inhibitory factor & Cytokine. The author has an hindex of 119, co-authored 595 publications receiving 54607 citations. Previous affiliations of Richard Bucala include École Polytechnique Fédérale de Lausanne & Rockefeller University.

ICBP90 Regulates MIF Expression, Glucocorticoid Sensitivity, and Apoptosis at the MIF Immune Susceptibility Locus.

Abstract: Objective Macrophage migration inhibitory factor (MIF) is an inflammatory and neurorendocrine mediator that counterregulates glucocorticoid immunosuppression. MIF polymorphisms, which comprise a variant promoter microsatellite (-794 CATT5-8 ), are linked genetically to autoimmune disease severity and to glucocorticoid resistance. While invasive stimuli increase MIF expression, MIF also is up-regulated by glucocorticoids, which serve as a physiologic regulator of inflammatory responses. This study was undertaken to define interactions between the MIF promoter, the glucocorticoid receptor (GR), and the transcription factor inverted CCAAT box binding protein 90 kd (ICBP90) (also referred to as UHRF1), which binds to the promoter in a -794 CATT5-8 length-dependent manner, to regulate MIF transcription. Methods Interactions of ICBP90, GR, and activator protein 1 (AP-1) with MIF -794 CATT5-8 promoter constructs were assessed by coimmunoprecipitation, Western blotting, and genetic knockdown. Nuclear colocalization studies were performed using anti-transcription factor antibodies and confocal microscopy of glucocorticoid-treated cells. MIF transcription was studied in CEM-C7 T cells, and the impact of the MIF -794 CATT5-8 microsatellite variation confirmed in peripheral blood T cells and in rheumatoid synovial fibroblasts of defined MIF genotype. Functional interactions were quantified by apoptosis and apoptotic signaling in high- and low-genotypic MIF-expressing human cells. Results We defined functional interactions between the transcription factors ICBP90, the GR, and AP-1 that up-regulated MIF transcription in a -794 CATT5-8 length-dependent manner. Experimental reduction of ICBP90, GR, or AP-1 decreased MIF expression and increased glucocorticoid sensitivity, leading to enhanced apoptosis in T lymphocytes and in rheumatoid synovial fibroblasts. Conclusion These findings suggest a mechanism for genetic variation of glucocorticoid-regulated MIF transcription, with implications for autoimmune disease severity and glucocorticoid responsiveness.

High expression of macrophage migration inhibitory factor in the murine lacrimal gland.

Abstract: Purpose To report the expression of macrophage migration inhibitory factor (MIF) in murine lacrimal glands. Methods Six lacrimal glands from 3 female 8-week-old CBA/J mice were analyzed using a gene microarray method (Oligo GEArray mouse inflammatory cytokines and receptors, Catalog No. OMM-011, SuperArray Bioscience) and immunofluorescent staining for MIF. Nine lacrimal glands from 8-week-old CBA/J mice, 9 lacrimal glands from 8-week-old C57BL/6 mice, and 7 lacrimal glands from 8-week-old BALB/c mice were analyzed using real-time reverse transcription-polymerase chain reaction. Five spleens, 5 livers, and 5 serum samples from 5 female 8-week-old CBA/J mice were analyzed using enzyme-linked immunosorbent assay. Results Microarray analysis revealed that MIF is highly expressed in the murine lacrimal gland. Lacrimal acinar cells stain strongly with anti-MIF antibodies. Real-time reverse transcription-polymerase chain reaction revealed that the MIF mRNA expression level is lower in lacrimal glands of CBA/J mice compared with C57BL/6 and BALB/c mice when normalized against the expression of beta-actin mRNA. Enzyme-linked immunosorbent assay revealed that MIF level was higher in lacrimal glands and spleens compared with livers and sera. Conclusion The murine lacrimal gland expresses high levels of macrophage MIF without any evidence of lacrimal gland inflammation.

Macrophage Migration Inhibitory Factor (MIF)

Abstract: This chapter provides an overview of macrophage migration inhibitory factor (MIF), which is a critical pro-inflammatory mediator that has been found to play an important role in diverse conditions characterized both by inflammation and cellular proliferation. MIF has a number of unique structural, genetic, and functional properties that distinguish it from other cytokines. These properties include unique tertiary structure, catalytic activity, a non-conventional secretory pathway, widespread expression and secretion from endocrine as well as immune cells, and its action as an endogenous counter-regulator of the anti-inflammatory and immunosuppressive properties of steroids. Also, MIF is unique in being a “pro-inflammatory” mediator that is induced in cells by glucocorticoids. Consistent with the wide range of activities of MIF, it has been found to be involved in the pathogenesis of many conditions. Important areas of future investigation includes in identifying the nature, and regulation of the MIF receptor, understanding the regulation of MIF at the genetic level, and designing clinically effective means of inhibiting its activity.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

Multilineage Potential of Adult Human Mesenchymal Stem Cells

Abstract: Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。