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Allison M Weis, Raymond Soto, June L Round
The commensal microbiota influences many aspects of immune system regulation, including T cells, but molecular details of how this occurs are largely unknown. Here we review our findings that the microbiota regulates Erdr1, a secreted apoptotic factor, to control T cell survival. Erdr1 is highly upregulated in CD4+ T cells from germfree mice and antibiotic treated animals, and our study shows that Erdr1 is suppressed by the microbiota via Toll-like receptor signaling and MyD88 dependent pathways. Erdr1 functions in an autocrine fashion and promotes apoptosis through the FAS/FASL pathway...
March 15, 2018: Gut Microbes
Rezvan Asgari, Kheirollah Yari, Kamran Mansouri, Mitra Bakhtiari
The interaction of FAS/FAS ligand (FASL) serves an important role in the upregulation of apoptotic processes through different mechanisms in cells. Previous studies have established that the polymorphisms FAS -670A/G and FASL -844C/T are associated with risk of generalized aggressive periodontitis (GAP) in different ethnic populations. Therefore, in the present study, it was investigated for the first time whether FAS -670A/G and FASL -844C/T polymorphisms were associated with risk of GAP in Iran. This case-control study performed the polymerase chain reaction-restriction fragment length polymorphism method in 25 patients with GAP and 110 normal subjects as controls...
April 2018: Biomedical Reports
Roberta Lotti, En Shu, Tiziana Petrachi, Alessandra Marconi, Elisabetta Palazzo, Marika Quadri, Ann Lin, Lorraine A O'Reilly, Carlo Pincelli
Pemphigus is a blistering disease characterized by pemphigus autoantibodies (PVIgG) directed mostly against desmogleins (Dsgs), resulting in the loss of keratinocyte adhesion (acantholysis). Yet, the mechanisms underlying blister formation remain to be clarified. We have shown previously that anti-Fas ligand (FasL) antibody (Ab) prevents PVIgG-induced caspase-8 activation and Dsg cleavage in human keratinocytes, and that sera from pemphigus patients contain abnormally increased levels of FasL. Here, we demonstrate that recombinant FasL induces the activation of caspases prior to Dsg degradation, and anti-FasL Ab prevents acantholysis in cultured keratinocytes...
2018: Frontiers in Immunology
Guolei Zhang, Junpu Zha, Junchuan Liu, Jun Di
One of the crucial mechanisms following spinal cord injury is mitochondria associated cell death. Minocycline, an anti-inflammatory drug is well known to impede the mitochondrial cell death. However, there has been no study on the effect of minocycline linking FAS-mediated cell death and hypoxia inducible factor (HIF-1α), the targets involved in mitochondrial cell death. Male Sprague Drawley rats (N = 18, divided into three groups) were subjected to traumatic spinal cord injury and were injected with minocycline (n = 6) (90 mg/kg, and later 45 mg/kg dose two times a day (every 12 h)...
March 9, 2018: Microbial Pathogenesis
Ying Liu, Lihong Ren, Wenjing Liu, Zhibo Xiao
MiR-21 has been found to be up-regulated in keloid tissue and affect the proliferation and apoptosis of keloid fibroblasts. However, the possible related mechanisms remain unclear. In this study, we aimed to evaluate the role of miR-21 in FasL-induced caspase-8 activation and mitochondrial-mediated apoptotic signaling pathway in keloid fibroblasts. According to the present study, the protein level of FasL was decreased by miR-21 overexpression, while enhanced by miR-21 inhibition in keloid fibroblasts. Subsequently, the mitochondrial-mediated apoptosis of keloid fibroblasts was restrained by miR-21 overexpression as evidenced by enhanced mitochondria membrane potential and decreased production of mitochondrial ROS...
March 10, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
Ilana C van Rensburg, Andre G Loxton
Regulatory B cells (Bregs) have been shown to be present during several disease states. The phenotype of the cells is not completely defined and the function of these cells differ between disease. The presence of FASL expressing (killer) B cells during latent and successfully treated TB disease have been shown but whether these cells are similar to regulatory B cells remain unclear. We assessed the receptor expression of FASL/IL5 (killer B cells), CD24/CD38 (regulatory B cells) on whole peripheral blood of participants with untreated active TB and healthy controls...
January 2018: Tuberculosis
Ruili Yang, Tingting Yu, Dawei Liu, Songtao Shi, Yanheng Zhou
BACKGROUND: Mesenchymal stem cells derived from gingiva (GMSCs) display profound immunomodulation properties in addition to self-renewal and multilineage differentiation capacities. Hydrogen sulfide (H2 S) is not only an environmental pollutant, but also is an important biological gas transmitter in health and disease. METHODS: We used an in-vitro coculture system and a mouse colitis model to compare the immunomodulatory effects between control and H2 S-deficient GMSCs...
March 9, 2018: Stem Cell Research & Therapy
Dan Gu, Lulin Huang, Xia Chen, Qianhu Wu, Kan Ding
A galactan ROH05 was isolated from the roots of Ophiopogon japonicus and further purified by DEAE Sepharose™ Fast Flow columns. The molecular weight of ROH05 was estimated to be 16.7 kDa. ROH05 was composed of galactose only. According to the methylation analysis and the results of IR and NMR spectra, the backbone of ROH05 was composed of 1, 4-linked β-D-galactose and 1, 4, 6-linked β-D-galactose, while the branch of this polysaccharide was terminal-linked β-D-galactose attached at C-6 position of 1, 4-linked β-D-galactose directly...
March 5, 2018: International Journal of Biological Macromolecules
Dan Li, Qing-Ling Li, Qiang Ma, Na-Na Liu, Jia-Hui Yang, Yong-Lei Zeng, Ling He, Hui Tan, Xue-Zhao Jia, Jing Wang
OBJECTIVE: To observe the effect of moxibustion on cardiac function and the expression of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X (Bax), Fas, Fas ligand (FasL) in cardiomyocytes of chronic heart failure (CHF) rats, so as to explore its underlying mechanisms in preventing and treating CHF. METHODS: SD rats were randomly divided into normal control, model, moxibustion, Captopril and moxibustion + Captopril (M+C) groups ( n =12 rats/group). The CHF model was established by intraperitoneal injection of Adriamycin (ADR, from 1 to 4 mg/kg, once every other day for 15 days)...
February 25, 2018: Zhen Ci Yan Jiu, Acupuncture Research
Jing Cao, Xiao-Ming Liu, Li-Lin Huang, Li Wang, Xiao-Fei Jiao, Li-Jun Huo
In the mammalian ovary, >99% follicles fail to ovulate due to apoptosis in granulosa cells. Aurora B, a core subunit enzyme of the chromosomal passenger complex, exerts a crucial role in microtubule‑kinetochore attachment, and has been reported to be modified by small ubiquitin‑related modifier (SUMO) proteins. However, the details of how Aurora B and its SUMOylation impact on follicular development have yet to be fully elucidated. The aim of the present study was to explore the roles, and possible molecular mechanism, of Aurora B and its SUMOylation in the granulosa cells of the mouse follicle...
March 7, 2018: International Journal of Molecular Medicine
André S Molina, João P Duprat Neto, Eduardo Bertolli, Isabela W da Cunha, José H T G Fregnani, Pedro H M Figueiredo, Fernando A Soares, Mariana P Macedo, Clovis A Pinto Lopes, Ivan D de Abranches Oliveira Santos Filho
BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare low grade tumor with a locally aggressive behavior and low metastatic potential. OBJECTIVES: To evaluate the factors that are associated with relapse in DFSP. Methods Retrospective analysis of medical records from 61 patients with dermatofibrosarcoma. Fluorescence in situ hybridization was used to detect translocations. RESULTS: Of 61 patients, 6 experienced a relapse. No patient with resection margins greater than 3 cm had a recurrence...
March 6, 2018: Journal of Surgical Oncology
Matthew A Lakins, Ehsan Ghorani, Hafsa Munir, Carla P Martins, Jacqueline D Shields
Tumours have developed strategies to interfere with most steps required for anti-tumour immune responses. Although many populations contribute to anti-tumour responses, tumour-infiltrating cytotoxic T cells dominate, hence, many suppressive strategies act to inhibit these. Tumour-associated T cells are frequently restricted to stromal zones rather than tumour islands, raising the possibility that the tumour microenvironment, where crosstalk between malignant and "normal" stromal cells exists, may be critical for T cell suppression...
March 5, 2018: Nature Communications
Honglan Qu, Wei Yang, Jie Li
In present study, we purified a polysaccharide, TFPB1, from the flower buds of Tussilago farfara using DEAE-cellulose 52 anion-exchange and Sephacryl S-300 HR gel filtration chromatography. TFPB1 was a homogeneous polysaccharide with a molecular weight of 37.8 kDa and composed of rhamnose, galacturonic acid, glucose, galactose, and arabinose, in a ratio of 13:13:1:7:12. Methylation and NMR results demonstrated that TFPB1 contained a rhamnogalacturonan I backbone consisting of a repeat disaccharide unit →4)-α-D -GalAp-(1 → 2)-α-L -Rhap-(1→, substituted by various type II arabinogalactan branches including terminal galactose, (1 → 3)-β-D -galactan and (1 → 5)-α-L -arabinan, attached to the O-4 of (1 → 2)-α-L -Rhap...
March 2, 2018: International Journal of Biological Macromolecules
Simone Wicki, Ursina Gurzeler, Nadia Corazza, Vera Genitsch, Wendy Wei-Lynn Wong, Thomas Kaufmann
Neutrophils are key players in the early defense against invading pathogens. Due to their potent effector functions, programmed cell death of activated neutrophils has to be tightly controlled; however, its underlying mechanisms remain unclear. Fas ligand (FASL/CD95L) has been shown to induce neutrophil apoptosis, which is accelerated by the processing of the BH3-only protein BH3 interacting domain death agonist (BID) to trigger mitochondrial apoptotic events, and been attributed a regulatory role during viral and bacterial infections...
February 28, 2018: International Journal of Molecular Sciences
Tzu-Ching Huang, Pu-Rong Chiu, Wen-Tsan Chang, Bau-Shan Hsieh, Yu-Ci Huang, Hsiao-Ling Cheng, Li-Wen Huang, Yu-Chen Hu, Kee-Lung Chang
Epirubicin is an anthracycline and is widely used in tumor treatment, but has toxic and undesirable side effects on wide range of cells and hematopoietic stem cells (HSC). Osteoblasts play important roles in bone development and in supporting HSC differentiation and maturation. It remains unknown whether epirubicin-induced bone loss and hematological toxicity are associated with its effect on osteoblasts. In primary osteoblast cell cultures, epirubicin inhibited cell growth and decreased mineralization. Moreover, epirubicin arrested osteoblasts in the G2/M phase, and this arrest was followed by apoptosis in which both the extrinsic (death receptor-mediated) and intrinsic (mitochondrial-mediated) apoptotic pathways were evoked...
February 21, 2018: Apoptosis: An International Journal on Programmed Cell Death
Dhivya Thiyagarajan, Hege L Pedersen, Natalya Seredkina, Kjersti D Horvei, Lorena Arranz, Ramon Sonneveld, Tom Nijenhuis, Johan van der Vlag, Ole P Rekvig
Recently we described that endonuclease inactive DNase I translocated into the nucleus in response to increased endogenous IL-1β expression. Here, we demonstrate impact and function of translocated DNase I in tubular cells. Effect of cytokines on expression level and nuclear localisation of DNase I and corresponding levels of Fas receptor (FasR) and IL-1β were determined by confocal microscopy, qPCR and western blot analyses, in presence or absence of siRNA against IL-1β and DNase I mRNA. Nuclear DNase I bound to the FAS promotor region as determined by chromatin immuno-precipitation analysis...
2018: Frontiers in Cell and Developmental Biology
Roman C Brands, Mario J J Scheurer, Stefan Hartmann, Axel Seher, Alexander C Kübler, Urs D A Müller-Richter
Inhibitor of apoptosis proteins, which are overexpressed in head and neck squamous cell carcinoma (HNSCC), may cause therapeutic resistance. Using SMAC mimetic compounds, including birinapant, to degrade and/or inhibit these proteins and sensitize apoptosis may enhance therapies in HNSCC. Fas expression was analyzed in nine HNSCC cell lines and one keratinocyte cell line via flow cytometry. These cell lines were treated with Fas ligand-Fc (FasL) and birinapant, a bivalent SMAC mimetic, in mono and combination therapies...
March 2018: Oncology Letters
Purnima Bhat, Anne-Sophie Bergot, Nigel Waterhouse, Ian Hector Frazer
Cervical cancer is a malignant transformation of keratinocytes initiated by the E7 oncoprotein of human papillomavirus (HPV). These tumors are characterized by keratinocyte hyperproliferation and are often infiltrated with activated CD8 T cells. HPV infection confers changes to gain immunological advantage to promote chronic infection, and these persist with malignant transformation. We investigated the relative importance of the many redundant mechanisms of cytotoxicity used by CD8 T cells to kill keratinocytes expressing HPV E7 oncoprotein using extended-duration time-lapse microscopy that allows examination of cell-to-cell interactions during killing...
January 19, 2018: Oncotarget
Cavit Ceylan, Sedat Yahşi, Serkan Doğan, Elife ÖztÜrk, Gulay Ceylan
BACKGROUND: Bladder cancer (BCa) is the seventh most common cancer among males worldwide. Some reliable markers in blood, urine, and tumor tissue, including clinicopathologic variables, molecular and inflammatory markers, gene polymorphisms, and tumor gene expression profiles are identified for predicting response to BCG immunotherapy in high-risk BCa patients. AIMS: We aimed to determine if FAS and FASL polymorphisms are associated with lack of response to BCG in patients with BCa...
February 16, 2018: Irish Journal of Medical Science
Xuanxuan Guo, Xiang Fang, Guodan He, M Haidar Zaman, Xibin Fei, Wei Qiao, Guo-Min Deng
Skin injury is the second most common clinical manifestation in patients with SLE. Neutrophils are crucial effector cells in immune system. The significance of neutrophils in the pathogenesis of SLE is not clear. This study is to explore the role of neutrophils in skin damage of SLE. We used lupus-prone mice and C57BL/6 mice model of lupus serum IgG induced skin inflammation to investigate neutrophils role in skin damage of SLE. We found a few neutrophils infiltrated in the inflammatory sites of skin in lupus-prone mice and lupus IgG induced skin damaged mice model...
February 16, 2018: Immunology
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