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Fabiana da Silva Lima, Amanda Batista da Rocha Romero, Araceli Hastreiter, Amanda Nogueira-Pedro, Edson Makiyama, Célia Colli, Ricardo Ambrósio Fock
Magnesium (Mg2+ ) is a mineral with the ability to influence cell proliferation and to modulate inflammatory/immune responses, due to its anti-inflammatory properties. In addition, mesenchymal stem cells (MSCs) modulate the function of all major immune cell populations. Knowing that, the current work aimed to investigate the effects of Mg2+ enrichment, and its influence on the immunomodulatory capacity of MSCs. Murine C3H/10T1/2 MSCs were cultivated in media with different concentrations of Mg2+ (0, 1, 3 and 5 mM), in order to evaluate the effects of Mg2+ on MSC immunomodulatory properties, cell proliferation rates, expression of NFκB and STAT-3, production of IL-1β, IL-6, TGF-β, IL-10, PGE2 and NO, and TRPM7 expression...
February 13, 2018: Journal of Nutritional Biochemistry
Judit Danis, Luca Janovák, Barbara Gubán, Anikó Göblös, Kornélia Szabó, Lajos Kemény, Zsuzsanna Bata-Csörgő, Márta Széll
Keratinocytes are non-professional immune cells contributing actively to innate immune responses partially by reacting to a wide range of molecular patterns by activating pattern recognition receptors. Cytosolic nucleotide fragments as pathogen- or self-derived trigger factors are activating inflammasomes and inducing anti-viral signal transduction pathways as well as inducing expression of inflammatory cytokines. We aimed to compare the induced inflammatory reactions in three keratinocyte cell types-normal human epidermal keratinocytes, the HaCaT cell line and the HPV-KER cell line-upon exposure to the synthetic RNA and DNA analogues poly(I:C) and poly(dA:dT) to reveal the underlying signaling events...
March 8, 2018: International Journal of Molecular Sciences
Carlene Petes, Mélissa K Mariani, Yawen Yang, Nathalie Grandvaux, Katrina Gee
Interleukin (IL)-30, the IL-27p28 subunit of the heterodimeric cytokine IL-27, acts as an antagonist of IL-27 and IL-6 signaling in murine cells via glycoprotein 130 (gp130) receptor and additional binding partners. Thus far, functions of IL-30 have not been fully elucidated in human cells. We demonstrate that like IL-27, IL-30 upregulated TLR4 expression to enhance lipopolysaccharide-induced TNF-α production in human monocytes; however, these IL-30-mediated activities did not reach the same levels of cytokine induction compared to IL-27...
2018: Frontiers in Immunology
Anthony J St Leger, Anna M Hansen, Hatice Karauzum, Reiko Horai, Cheng-Rong Yu, Arian Laurence, Katrin D Mayer-Barber, Phyllis Silver, Rafael Villasmil, Charles Egwuagu, Sandip K Datta, Rachel R Caspi
Appropriate regulation of IL-17 production in the host can mean the difference between effective control of pathogens and uncontrolled inflammation that causes tissue damage. Investigation of conventional CD4+ T cells (Th17 cells) has yielded invaluable insights into IL-17 function and its regulation. More recently, we and others reported production of IL-17 from innate αβ+ T cell populations, which was shown to occur primarily via IL-23R signaling through the transcription factor STAT-3. In our current study, we identify promyelocytic leukemia zinc finger (PLZF)-expressing iNKT, CD4- /CD8+ , and CD4- /CD8- (DN) αβ+T cells, which produce IL-17 in response to TCR and IL-1 receptor ligation independently of STAT-3 signaling...
February 28, 2018: Journal of Experimental Medicine
Zhixi Li, Wenjun Jiang, Gang Wu, Xueming Ju, Youyu Wang, Wenying Liu
The identification and development of novel therapeutic strategies for acute lung injury is urgently required. It has been previously demonstrated that microRNA (miR)‑16 suppresses the level of transforming growth factor (TGF)‑β in acute lung injury (ALI). Therefore, the present study investigated the role of miR‑16 in the phenotype, cell proliferation and apoptosis, and the involvement of TGF‑β/Smad family member 2 (Smad2) and JAK/signal transducer and activator of transcription (STAT)3 signaling, of primary human alveolar type II epithelial cells (AECII)...
February 26, 2018: Molecular Medicine Reports
Maliha A Alikhan, Megan Huynh, A Richard Kitching, Joshua D Ooi
The kidney is vulnerable to injury, both acute and chronic from a variety of immune and metabolic insults, all of which at least to some degree involve inflammation. Regulatory T cells modulate systemic autoimmune and allogenic responses in glomerulonephritis and transplantation. Intrarenal regulatory T cells (Tregs), including those recruited to the kidney, have suppressive effects on both adaptive and innate immune cells, and probably also intrinsic kidney cells. Evidence from autoimmune glomerulonephritis implicates antigen-specific Tregs in HLA-mediated dominant protection, while in several human renal diseases Tregs are abnormal in number or phenotype...
2018: Clinical & Translational Immunology
Hongyan Wen, Yang Liu, Jinchan Li, Dandan Wei, Dandan Liu, Fangfang Zhao
OBJECTIVES: To explore the inhibitory effect and mechanism of 1,25-dihydroxy vitamin D3 (l,25(OH)2D3) on receptor activator of nuclear factor-κB ligand (RANKL) expression in fibroblast-like synoviocytes (FLSs) and osteoclastogenesis induced by interleukin (IL)-22 in patients with rheumatoid arthritis (RA). METHODS: Fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA-FLSs) were cultured and stimulated for RANKL expression with IL-22 in the absence or presence of various concentrations of l,25(OH)2D3, and JAK-2 inhibitor or p38 MAPK inhibitor at the optimised time point of IL-22 treatment...
February 15, 2018: Clinical and Experimental Rheumatology
Su Tu, Feng Xiao, Xiaoyan Min, Huiping Chen, Xiaochun Fan, Kejiang Cao
Accumulating evidence has established that systemic inflammation is an important pathophysiologic factor of coronary heart disease (CHD). In this study, we investigated whether catechin exerts anti-inflammatory function in CHD rats. CHD model of rats was established by high-fat diet feeding and pituitrin injection. The successful building of CHD model was confirmed using blood liquid biochemical analyzer. Additionally, the effects of catechin on CHD parameters and several inflammatory signaling were investigated...
February 20, 2018: Cardiovascular Toxicology
Kyung Mok Kim, Ki Wung Chung, Hyeong Oh Jeong, Bonggi Lee, Dae Hyun Kim, June Whoun Park, Seong Min Kim, Byung Pal Yu, Hae Young Chung
Age-associated renal fibrosis is related with renal function decline during aging. Imbalance between accumulation and degradation of extracellular matrix is key feature of fibrosis. In this study, RNA-sequencing (RNA-Seq) results based on next-generation sequencing (NGS) data were analyzed to identify key proteins that change during aging and calorie restriction (CR). Among the changed genes, A2M and MMP2, which are known to interact, exhibited the highest between centrality (BC) and degree values when analyzed by protein-protein interaction (PPI)...
January 19, 2018: Oncotarget
Meihua Sun, Yuanyuan Huang, Feng Li, Haibo Li, Bo Zhang, Lianhua Jin
Pro-inflammatory cytokines-induced airway remodeling was a significant feature of asthma disease. The aim of the present study was to explore the functional significance of miR-874 in tumor necrosis factor (TNF)-α-treated human fetal airway smooth muscle (fASM) cells. Here, we found that TNF-α treatment significantly down-regulated the expression of miR-874 in fASM cells. MiR-874 overexpression markedly inhibited cell viability and migration, suppressed the expression of PCNA and Ki67, reduced the expression of collagen I and collagen III, decreased the expression and activity of matrix metalloproteinase (MMP)-9 and MMP-2, and induced an obvious elevation of tissue inhibitors of metalloproteinases (TIMPs)...
February 12, 2018: Respiratory Physiology & Neurobiology
Rob Houtmeyers, Jabob Souopgui, Sabine Tejpar
In the last decade, the amount of investigations on the involvement of ZIC genes in the cancer field have exponentially expanded. In most cancer types, promoter methylation leads to silenced ZIC family members, but specific subsets of patients clearly show increased expression of one or head-to-head located ZIC genes in the respective tumor tissue. It is unclear at this stage how these transcription factors contribute to tumorigenesis, but the potential implications in pathways that are most frequently mutated in cancer such as the canonical Wnt, TGF-beta, and STAT-3 pathway are evident...
2018: Advances in Experimental Medicine and Biology
Yu-Kyoung Park, Brice Wilfried Obiang-Obounou, Kyung-Bok Lee, Jong-Soon Choi, Byeong-Churl Jang
The proviral integration moloney murine leukaemia virus (Pim) kinases, consisting of Pim-1, Pim-2 and Pim-3, are involved in the control of cell growth, metabolism and differentiation. Pim kinases are emerging as important mediators of adipocyte differentiation. AZD1208 is a pan-Pim kinase inhibitor and is known for its anti-cancer activity. In this study, we investigated the effect of AZD1208 on adipogenesis and lipolysis in 3T3-L1 cells, a murine preadipocyte cell line. AZD1208 markedly suppressed lipid accumulation and reduced triglyceride contents in differentiating 3T3-L1 cells, suggesting the drug's anti-adipogenic effect...
February 14, 2018: Journal of Cellular and Molecular Medicine
Wanlu Li, Mi-Ra Lee, Taeyeong Kim, Young Wan Kim, Mee-Yon Cho
The activation of signal transducer and activator of transcription 3 (STAT3) by elevated interleukin (IL) levels has been reported to regulate tumorigenesis both in vitro and in vivo. However, the clinical implication of p-STAT3 expression in colon cancer is still controversial. In this study, we evaluated the effect of STAT3 inactivation on biologic behavior of primary (Caco-2) and metastatic colon cancer cells (LoVo and SNU407) and the relation of p-STAT3 expression with the invasion of colon tumor. In vitro study, the STAT3 inhibition by siRNA and stattic treatment significantly reduced colony formation and cell migration and decreased CD133 and survivin the expression compared with a control in all three cell lines...
February 9, 2018: Biochemical and Biophysical Research Communications
Zheng-Wei Fu, Zhen-Yu Zhang, Hai-Yan Ge
Efficient delivery routes are critical for the effectiveness of adipose-derived mesenchymal stem cells (ADMSCs) in treating inflammatory bowel disease (IBD). Conventional ADMSC delivery routes include local, intravenous and intraperitoneal injection. Whether mesenteric injection has potential in IBD treatment remains unknown. In the present study, we investigated the therapeutic effects of mesenteric injection of ADMSCs in a trinitrobenzene sulfonic acid-induced rat IBD model and explored whether this treatment affected T helper 17 (Th17)/regulatory T (Treg) cell ratio...
2018: American Journal of Translational Research
Cody McHale, Zahraa Mohammed, Juline Deppen, Gregorio Gomez
BACKGROUND: Interleukin-6 is a gp130 utilizing cytokine that is consistently associated with allergic diseases like asthma and urticaria in humans where mast cells are known to play a critical role. However, the role of IL-6 in allergic disease in not known. IL-6 was reported to enhance degranulation of in vitro-derived mast cells, but the effect of IL-6 on mediator release from human in situ-matured tissue-isolated mast cells had not been reported. METHODS: Human mature mast cells were isolated and purified from normal skin tissue from different donors...
February 1, 2018: Biochimica et Biophysica Acta
Sung Ho Kim, Hyo Soon Yoo, Moon Kyung Joo, Taehyun Kim, Jong-Jae Park, Beom Jae Lee, Hoon Jai Chun, Sang Woo Lee, Young-Tae Bak
BACKGROUND: We investigated the effect of arsenic trioxide (ATO) for inhibition of signal transducer and activator of transcription 3 (STAT3) and epithelial-mesenchymal transition (EMT) in gastric cancer cells, and the role of SH2 domain-containing phosphatase-1 (SHP-1) during this process. METHODS: We used AGS cells, which showed minimal SHP-1 expression and constitutive STAT3 expression. After treatment of ATO, cellular migration and invasion were assessed by using wound closure assay, Matrigel invasion assay and 3-D culture invasion assay...
February 6, 2018: BMC Cancer
Lijun Xu, Mingjing Shen, Xiaodong Chen, Dong-Rong Yang, Ying Tsai, Peter C Keng, Soo Ok Lee, Yuhchyau Chen
Previous reports, including our experimental results, showed that macrophages migrate to prostate cancer (PCa) cells. We tested whether the migrated macrophages affect the susceptibility of castration-resistant PCa (CRPC) cells to cytotoxic actions of natural killer (NK) cells. We found treatment of tumor cells with the conditioned media (CM) of the PMA/IL-4 treated THP-1 cells (M2 type macrophages) (THP-1 CM) decreased the susceptibility of tumor cells to NK cell cytotoxicity, as a result of increased programmed death receptor ligand 1 (PD-L1) and decreased NK group 2D (NKG2D) ligands in CRPC cells...
January 31, 2018: Experimental Cell Research
Shanshan Hu, Cameron Marshall, Jocelyn Darby, Wei Wei, Alan Bruce Lyons, Heinrich Körner
The absence of tumor necrosis factor (TNF) causes lethal infection by Leishmania major in normally resistant C57BL/6J (B6.WT) mice. The underlying pathogenic mechanism of this fatal disease has so far remained elusive. We found that B6.WT mice deficient for the tnf gene (B6.TNF-/-) displayed not only a non-healing cutaneous lesion but also a serious infection of the liver upon L. major inoculation. Infected B6.TNF-/- mice developed an enlarged liver that showed increased inflammation. Furthermore, we detected an accumulating monocyte-derived macrophage population (CD45+F4/80+CD11bhiLy6Clow) that displayed a M2 macrophage phenotype with high expression of CD206, arginase-1, and IL-6, supporting the notion that IL-6 could be involved in M2 differentiation...
2018: Frontiers in Immunology
Hiroshi Kanno, Yuqun Xu, Taykua Miyakawa, Atsuhiko Kubo, Tetsuhiro Higashida, Nahoko Baily Kobayashi, Tetsuhiko Yoshida, Masaru Tanokura
Von Hippel-Lindau tumor suppressor protein (pVHL) functions to induce neuronal differentiation of neural stem/progenitor cells (NSCs) and skin-derived precursors (SKPs). Here we identified a neuronal differentiation domain (NDD) in pVHL. Neuronal differentiation of SKPs was induced by intracellular delivery of a peptide composed of the amino-acid sequences encoded by the NDD. Neuronal differentiation mediated by the NDD was caused by the binding between it and elongin C followed by Janus kinase-2 (JAK2) ubiquitination of JAK2 and inhibition of the JAK2/the signal transducer and activator of transcription-3(STAT)3 pathway...
February 5, 2018: International Journal of Molecular Sciences
Qingxia Xu, Liang Li, Cuihong Han, Li Wei, Lingling Kong, Fanzhong Lin
Sigma-1 receptor (σ1R), an important transmembrane structural protein, has been demonstrated to be overexpressed in various types of human cancer, and has been confirmed to be involved in many biological behaviors during tumorigenesis and tumor progression. The aim of the present study was to explore the essential role of σ1R in hepatic malignant tumors (HMTs), which, to the best of our knowledge, has not been reported to date. We assessed σ1R expression in hepatocellular carcinoma (HCC) tissues and found that σ1R was significantly decreased in HCC when compared with that in benign liver tissues (P<0...
January 22, 2018: Oncology Reports
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