The Role of Lysosomes in Molluscan Inflammation1

Phagocytosis and related phenomena represent integral featuresof inflammation in all metazoans. Reviewed herein are the resultsof studies directed at understanding the role(s) of lysosomalenzymes synthesized and released from circulating hemocytes,especially granulocytes, of gastropods and bivalves as a resultof challenge with exogenous, nonself materials. From what isknown, most of the mechanisms underlying this inflammation-associatedprocess parallel those of mammalian macrophages; however, immunoglobulinsand most probably components of complement are not involved.The required energy for phagocytosis in molluscs appears tobe derived from glycolysis alone. Furthermore, nitroblue tetrazoliumreduction and the myeloperoxidase-H₂O₂-halide antimicrobialsystem, both characteristic of mammalian phagocytes, appearto be absent in molluscs. It is concluded that by studying phagocytosisby molluscan hemocytes, a great deal can be learned about theevolution of inflammatory response and its constitutent elements.     

Diverse Regulation of YB-1 and YB-3 Abundance in Mammals

Biochemistry (Moscow) - YB proteins are DNA/RNA binding proteins, members of the family of proteins with cold shock domain. Role of YB proteins in the life of cells, tissues, and whole organisms is...     

Host-Derived Smooth Muscle Cells Accumulate in Cardiac Allografts: Role of Inflammation and Monocyte Chemoattractant Protein 1

Transplant arteriosclerosis is characterized by inflammation and intimal thickening caused by accumulation of smooth muscle cells (SMCs) both from donor and recipient. We assessed the relationship between clinical factors and the presence of host-derived SMCs in 124 myocardial biopsies from 26 consecutive patients who received hearts from opposite-sex donors. Clinical and demographic information was obtained from the patients'' medical records. Host-derived SMCs accounted for 3.35±2.3% of cells in arterioles (range, 0.08–12.51%). As shown by linear regression analysis, an increased number of SMCs was associated with rejection grade (mean, 1.41±1.03, p = 0.034) and the number of leukocytes (19.1±12.7 per 20 high-power fields, p = 0.01). The accumulation of host-derived SMCs was associated with an increased number of leukocytes in the allografts. In vitro, monocyte chemoattractant protein 1 (MCP-1) released from leukocytes was crucial for SMC migration. After heart allotransplantion, mice treated with MCP-1-specific antibodies had significantly fewer host-derived SMCs in the grafts than mice treated with isotypic antibody controls. We conclude that the number of host-derived SMCs in human cardiac allografts is associated with the rejection grade and that MCP-1 may play pivotal role in recruiting host-derived SMCs into cardiac allografts.     

Application of Monoclonal Antibodies and Phage Display Technology for YB-1 Protein Analysis

Russian Journal of Bioorganic Chemistry - Monoclonal antibodies against the recombinant YB-1 protein were obtained and characterized. These antibodies are capable of specific detection of YB-1...     

YB-1 Protein in Breast Cancer (Scientific and Personal Meetings with Professor Ovchinnikov)

Biochemistry (Moscow) - In the article, the author examines the properties of Y-box-binding protein (YB-1) and expression of the YBX-1 gene in various malignant tumors and provides the data from...     

FoxO1在病毒感染和炎症发生中的作用

FoxO1是Foxs家族的成员,该家族大多数为转录因子.FoxO1作为Foxs家族的重要转录因子之一,它不仅具有调控转录的作用,也参与许多生理过程,例如糖代谢、细胞凋亡、脂肪代谢、肌细胞的分化、生殖和肿瘤的发生等.近些年,也有越来越多的研究证实FoxO1在病毒感染和炎症发生等过程也具有重要作用,但其中机制还不清楚.本文主要讲述了几种病毒感染及炎症发生期间,FoxO1在其中发挥的重要作用.     

冷诱导RNA结合蛋白在急性脑外伤后的表达变化及其促炎作用研究

目的:观察小鼠急性脑外伤后,冷诱导RNA结合蛋白(CIRP)的表达变化情况及其对炎症因子的影响,旨在探讨CIRP在神经系统损伤性疾病中的作用,为该疾病的临床治疗提供新的思路。方法:成年小鼠随机分为正常组(n=10)和手术组(n=36),用液压打击法建立小鼠急性脑外伤模型,利用HE染色法观察模型建立后小鼠大脑的损伤情况;损伤后24、48 h时间点,采用实时PCR检测大脑损伤部位CIRP和炎症因子肿瘤坏死因子α(TNFα)m RNA的表达,免疫组织化学法检测CIRP蛋白水平的表达;分析CIRP表达变化与炎症因子TNFα相关性。结果:急性脑外伤后小鼠脑损伤部位的CIRP m RNA及蛋白表达水平呈上升趋势,CIRP表达与炎症因子TNFα表达正相关。结论:CIRP可能参与了小鼠脑外伤的炎性反应过程。     

Phosphorylation of Mitogen- and Stress-Activated Protein Kinase-1 in Astrocytic Inflammation: A Possible Role in Inhibiting Production of Inflammatory Cytokines

Purpose

It is generally accepted that inflammation has a role in the progression of many central nervous system (CNS) diseases, although the mechanisms through which this occurs remain unclear. Among mitogen-activated protein kinase (MAPK) targets, mitogen- and stress-activated protein kinase (MSK1) has been thought to be involved in the pathology of inflammatory gene expression. In this study, the roles of MSK1 activation in neuroinflammation were investigated.

Methods

The bacterial lipopolysaccharide (LPS)-induced brain injury model was performed on Sprague-Dawley rats. The dynamic expression changes and the cellular location of p-MSK1 in the brain cortex were detected by Western blot and immunofluorescence staining. The synthesis of inflammatory cytokines in astrocytes was detected by enzyme-linked immunosorbent assay (ELISA).

Results

Phosphorylated MSK1 (p-MSK1 Thr-581) was induced significantly after intracerebral injection of LPS into the lateral ventricles of the rat brain. Specific upregulation of p-MSK1 in astrocytes was also observed in inflamed cerebral cortex. At 1 day after LPS stimulation, iNOS, TNFα expression, and the astrocyte marker glial fibrillary acidic protein (GFAP) were increased significantly. Also, in vitro studies indicated that the upregulation of p-MSK1 (Thr-581) may be involved in the subsequent astrocyte inflammatory process, following LPS challenge. Using an enzyme-linked immunosorbent assay (ELISA), it was confirmed that treatment with LPS in primary astrocytes stimulated the synthesis of inflammatory cytokines, through MAPKs signaling pathways. In cultured primary astrocytes, both knock-down of total MSK1 by small interfering RNAs (siRNA) or specific mutation of Thr-581 resulted in higher production of certain cytokines, such as TNFα and IL-6.

Conclusions

Collectively, these results suggest that MSK1 phosphorylation is associated with the regulation of LPS-induced brain injury and possibly acts as a negative regulator of inflammation.     

蛋白激酶PINK1与炎症及免疫反应

磷酸酶及张力蛋白同源物诱导的蛋白激酶1(PTEN induced putative kinase 1, PINK1) 是一种与线粒体自噬、帕金森病的发生发展密切相关的蛋白激酶。PINK1蛋白由581个氨基酸残基组成,具有高度保守的结构域,表达广泛。除了帕金森病,PINK1还参与多种疾病的发生、发展和调控,如肿瘤、糖尿病、心肺功能异常等。近年的研究表明,PINK1的表达影响T细胞的增殖和分化,抑制线粒体抗原递呈,参与调节机体固有免疫反应和炎症反应。另外,炎症小体NLRP3对肺内皮细胞的调节作用也与PINK1表达有关。PINK1也能通过NLRP3调节炎症介质的释放,参与脓毒症诱导的免疫代谢活动。本文就近年来PINK1与炎症、免疫反应的相关研究进行综述。     

Temporal Changes in Glutaredoxin 1 and Protein S-Glutathionylation in Allergic Airway Inflammation

Introduction

Asthma is a chronic inflammatory disorder of the airways, involving oxidative stress. Upon oxidative stress, glutathione covalently binds to protein thiols to protect them against irreversible oxidation. This posttranslational modification, known as protein S-glutathionylation, can be reversed by glutaredoxin 1 (Glrx1) under physiological condition. Glrx1 is known to increase in the lung tissues of a murine model of allergic airway inflammation. However, the temporal relationship between levels of Glrx1, protein S-glutathionylation, and glutathione in the lungs with allergic airway inflammation is not clearly understood.

Methods

BALB/c mice received 3 aerosol challenges with ovalbumin (OVA) following sensitization to OVA. They were sacrificed at 6, 24, 48, or 72 h, or 8 days (5 mice per group), and the levels of Glrx1, protein S-glutathionylation, glutathione, and 25 cytokines/chemokines were evaluated in bronchoalveolar lavage fluid (BALF) and/or lung tissue.

Results

Levels of Glrx1 in BALF were significantly elevated in the OVA 6 h (final challenge) group compared to those in the control, with concurrent increases in protein S-glutathionylation levels in the lungs, as well as total glutathione (reduced and oxidized) and oxidized glutathione in BALF. Protein S-glutathionylation levels were attenuated at 24 h, with significant increases in Glrx1 levels in lung tissues at 48 and 72 h. Glrx1 in alveolar macrophages was induced after 6 h. Glrx1 levels concomitantly increased with Th2/NF-κB-related cytokines and chemokines in BALF.

Conclusions

The temporal relationships of Glrx1 with protein S-glutathionylation, glutathione, and cytokines/chemokines were observed as dynamic changes in lungs with allergic airway inflammation, suggesting that Glrx1 and protein–SSG redox status may play important roles in the development of allergic airway inflammation.     

YB-1与EGFR在子宫内膜异位症中表达的研究进展

YB-1,EGFR各自作为冷激蛋白和糖蛋白家族的成员表达于各种生理和环境的损伤之后,保护细胞的生存。近年来发现YB-1和EGFR在多种癌症及内异症中高表达,并且参与肿瘤和子宫内膜异位组织的发生,发展,分化及转移的各个方面。因而YB-1和EGFR的高表达能影响子宫内膜异位症的发生和发展;也说明YB-1和EGFR可以作为子宫内膜异位症患者一个潜在的诊断和治疗靶点。     

Role of the Liver in Inflammation

INFLAMMATION leads to the appearance in plasma and inflammatory exudates of a protein with anti-inflammatory properties^1–4. The greatest concentration of this anti-inflammatory protein (AIP) occurs relatively late after injury², which suggests that it plays a role in the later stages of the inflammatory reaction and during healing. The synthesis of the protein is shown here to be similar to that of most other plasma proteins in that it occurs in the liver, which raises the question of the extent to which inflammation is influenced or controlled by the rates of synthesis of plasma proteins.     

Role of TREM1-DAP12 in Renal Inflammation during Obstructive Nephropathy

Tubulo-interstitial damage is a common finding in the chronically diseased kidney and is characterized by ongoing inflammation and fibrosis leading to renal dysfunction and end-stage renal disease. Upon kidney injury, endogenous ligands can be released which are recognized by innate immune sensors to alarm innate immune system. A new family of innate sensors is the family of TREM (triggering receptor expressed on myeloid cell). TREM1 is an activating receptor and requires association with transmembrane adapter molecule DAP12 (DNAX-associated protein 12) for cell signaling. TREM1-DAP12 pathway has a cross-talk with intracellular signaling pathways of several Toll-like receptors (TLRs) and is able to amplify TLR signaling and thereby contributes to the magnitude of inflammation. So far, several studies have shown that TLRs play a role in obstructive nephropathy but the contribution of TREM1-DAP12 herein is unknown. Therefore, we studied TREM1 expression in human and murine progressive renal diseases and further investigated the role for TREM1-DAP12 by subjecting wild-type (WT), TREM1/3 double KO and DAP12 KO mice to murine unilateral ureter obstruction (UUO) model. In patients with hydronephrosis, TREM1 positive cells were observed in renal tissue. We showed that in kidneys from WT mice, DAP12 mRNA and TREM1 mRNA and protein levels were elevated upon UUO. Compared to WT mice, DAP12 KO mice displayed less renal MCP-1, KC and TGF-β1 levels and less influx of macrophages during progression of UUO, whereas TREM1/3 double KO mice displayed less renal MCP-1 level. Renal fibrosis was comparable in WT, TREM1/3 double KO and DAP12 KO mice. We conclude that DAP12, partly through TREM1/3, is involved in renal inflammation during progression of UUO.     

Role of YB-1 in Regulation of Poly(ADP-Ribosylation) Catalyzed by Poly(ADP-Ribose) Polymerases

Biochemistry (Moscow) - Poly(ADP-ribosyl)ation is a post-translational modification of proteins that performs an essential regulatory function in the cellular response to DNA damage. The key enzyme...