[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

Interferon-gamma (IFN-gamma) coordinates a diverse array of cellular programs through transcriptional regulation of immunologically relevant genes. This article reviews the current understanding of IFN-gamma ligand, receptor, signal transduction, and cellular effects with a focus on macrophage responses and to a lesser extent, responses from other cell types that influence macrophage function during infection. The current model for IFN-gamma signal transduction is discussed, as well as signal regulation and factors conferring signal specificity. Cellular effects of IFN-gamma are described, including up-regulation of pathogen recognition, antigen processing and presentation, the antiviral state, inhibition of cellular proliferation and effects on apoptosis, activation of microbicidal effector functions, immunomodulation, and leukocyte trafficking. In addition, integration of signaling and response with other cytokines and pathogen-associated molecular patterns, such as tumor necrosis factor-alpha, interleukin-4, type I IFNs, and lipopolysaccharide are discussed.

https://jlb.onlinelibrary.wiley.com/doi/epdf/10.1189/jlb.0603252

Interferon-γ: an overview of signals, mechanisms and functions

Publisher Summary This chapter discusses the role of plasminogen activators in various biological processes. In specific, it describes two types of plasminogen activators—namely, the urokinase-type plasminogen activator (u-PA) and the tissue-type plasminogen activator (t-PA), which are essentially different gene products. The amino acid sequences of these activators and nucleotide sequences of the corresponding cDNAs have largely been determined, and the cDNAs have been cloned using recombinant techniques. A variety of enzymatic as well as immunological assay and detection methods have also been developed that allows a precise quantification of the activators, a distinction between u-PA and t-PA, determination of whether an activator is present in its active or zymogen form, analysis of the kinetics of different steps of the cascade reaction, and immunocytochemical identification of u-PA and t-PA in tissue sections. Much of the studies on plasminogen activators and cancer has been guided by the hypothesis that proteolysis of the components of extracellular matrix, initiated by the release of plasminogen activator from the cancer cells, plays a decisive role for the degradation of normal tissue, and thereby for invasive growth and metastases.

Plasminogen activators, tissue degradation, and cancer.

The biochemistry and medical significance of the flavonoids.

Death by apoptosis is characteristic of cells undergoing deletion during embryonic development, T- and B-cell maturation and endocrine-induced atrophy. Apoptosis can be initiated by various agents and may be a result of expression of the oncosuppressor gene p53 (refs 6-8). Here we study the dependence of apoptosis on p53 expression in cells from the thymus cortex. Short-term thymocyte cultures were prepared from mice constitutively heterozygous or homozygous for a deletion in the p53 gene introduced into the germ line after gene targeting. Wild-type thymocytes readily undergo apoptosis after treatment with ionizing radiation, the glucocorticoid methylprednisolone, or etoposide (an inhibitor of topoisomerase II), or after Ca(2+)-dependent activation by phorbol ester and a calcium ionophore. In contrast, homozygous null p53 thymocytes are resistant to induction of apoptosis by radiation or etoposide, but retain normal sensitivity to glucocorticoid and calcium. The time-dependent apoptosis that occurs in untreated cultures is unaffected by p53 status. Cells heterozygous for p53 deletion are partially resistant to radiation and etoposide. Our results show that p53 exerts a significant and dose-dependent effect in the initiation of apoptosis, but only when it is induced by agents that cause DNA-strand breakage.

Thymocyte apoptosis induced by p53-dependent and independent pathways

Effect of estradiol-17β on PGF and total protein content in bovine uterine flushings and peripheral plasma concentration of 13, 14-dihydro-15-keto-PGF2α

Qualitative changes in the protein content of mare uterine flushings were determined on Days 4, 8, 12, 14, 16, 18 and 20 postovulation. Acid phosphatase and leucine aminopeptidase enzymatic activities were also determined for these treatment days. All collections were obtained using a nonsurgical, transcervical technique. Sephadex C-200 column chromatography indicated that 5 distinct protein fractions existed for all days tested. The chromatographic mobility (Kay) of these fractions did not change during the estrous cycle. When expressed as percentage of the total protein, peaks I, IV and V were significantly affected (P<0.005, 0.05 and 0.025, respectively) by day of the estrous cycle, whereas, peaks II and III were not. Acid phosphatase activity was significantly affected P<0.05) by day of the estrous cycle and maximal values were found in the late luteal phase. Mean values ranged from 10 to 193 �zM of inorganic phosphate released per h on Days 4 and 18, respectively, followed by a rapid decline on Day 20. Sephadex G-200 studies indicated that the acid phosphatase enzymatic activity was associated with low molecular weight fractions III and IV and, therefore, was probably nonlysosomal in origin. Leucine aminopeptidase activity was maximal in the midluteal phase (Day 12) and was significantly affected (P<O.005) by day of the estrous cycle. Sephadex G-200 chromatography indicated that this enzyme was associated with high molecular weight fractions I and II. Over the course of this study a purple-colored protein was found in the uterine flushing of a pseudopregnant mare. Biochemical and immunological examinations indicated that similar properties existed for the equine purple protein and the porcine purple protein, previously described

/pdf/uterine-luminal-proteins-in-the-cycling-mare-4g8pn6yvd3.pdf

Uterine Luminal Proteins in the Cycling Mare

Exocrine versus endocrine secretion of prostaglandin F2α in the control of pregnancy in swine

Uterine luminal fluids (ULF) from Large White (LW) and prolific Chinese Meishan (MS) gilts were compared with respect to their peptide growth factor content during an estrous cycle and early pregnancy. Insulin-like growth factor-I (IGF-I) was quantitated by RIA; in vitro growth promoting properties of uterine luminal fluid mitogen (ULFM) were measured by [3H]thymidine incorporation into DNA of quiescent AKR-2B fibroblastic cells in culture. Peak concentrations (pg/microgram ULF protein) of IGF-I in ULF of Large White and Meishan gilts, respectively, were: estrous cycle, 9.8 +/- 1.4 (on d 10) and 39.7 +/- 7.8 (on d 12); gestation, 13.1 +/- 3.2 (on d 8 and 10) and 11.9 +/- 2.1 (on d 12), with differences among days (except d 10, P greater than .5) being affected by breed (P less than .10). For both breeds, there was a rapid decline in IGF-I concentrations by d 14 of the cycle and of pregnancy. Uterine luminal fluid mitogen activity was greater (P less than .01) for LW than for MS gilts on d 10 to 14 of an estrous cycle and gestation and diminished in a time-dependent manner in both breeds. No correlation was observed between IGF-I concentrations and uterine weights for either breed. In contrast, a negative correlation between uterine weight and ULFM activity was detected for cyclic (MS: r = -.855, P less than .10; LW: r = -.834, P less than .05) and pregnant (MS: r = -.806, P less than .10; LW: r = -.928, P less than .05) gilts.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential Growth Factor Content of Uterine Luminal Fluids from Large White and Prolific Meishan Pigs during the Estrous Cycle and Early Pregnancy

Type I IFNs have a broad array of immunoregulatory functions that include up-regulation of type 1 immune responses through enhancing differentiation and activation of CD8+ T cells and CD4+ Th1 cells. Ovine trophoblast IFN-tau is a recently described type I IFN with the potential for therapeutic use, based on its potent antiviral activity yet low toxicity. Studies were designed to determine the immunoregulatory effects of IFN-tau on Ag-stimulated T cells, and a novel effect of type I IFNs on gammadelta T cells was observed. In cultures of parasite Ag-stimulated bovine T cells that contained a mixture of alphabeta and gammadelta T cells, both IFN-tau and IFN-alpha suppressed the expansion of WC1+ CD2- CD6- CD8- gammadelta T cells, yet stimulated the growth of WC1- CD2+ CD6+ CD8+ gammadelta T cells and CD8+ alphabeta T cells. The CD8+ gammadelta T cell subset expressed high levels of the IL-2R alpha-chain. Furthermore, we showed that type I IFN enhanced IL-2 production by these Ag-stimulated T cell lines. In short term cultures of PBMC, IL-2 stimulated an expansion of WC1- CD6+ CD8+ gammadelta T cells, which was significantly increased by IFN-tau, even though IFN-tau alone did not support cell survival. These studies demonstrate for the first time that type I IFNs differentially modulate the proliferation of different subsets of gammadelta T cells, which appears to act in part via IL-2.

Fuller W. Bazer

Papers

Effect of estradiol-17β on PGF and total protein content in bovine uterine flushings and peripheral plasma concentration of 13, 14-dihydro-15-keto-PGF2α

Uterine Luminal Proteins in the Cycling Mare

Exocrine versus endocrine secretion of prostaglandin F2α in the control of pregnancy in swine

Differential Growth Factor Content of Uterine Luminal Fluids from Large White and Prolific Meishan Pigs during the Estrous Cycle and Early Pregnancy

Differential effects of type i ifns on the growth of wc1- cd8+ gamma delta t cells and wc1+ cd8- gamma delta t cells in vitro