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Annamaria Cattaneo, Nadia Cattane, Samantha Galluzzi, Stefania Provasi, Nicola Lopizzo, Cristina Festari, Clarissa Ferrari, Ugo Paolo Guerra, Barbara Paghera, Cristina Muscio, Angelo Bianchetti, Giorgio Dalla Volta, Marinella Turla, Maria Sofia Cotelli, Michele Gennuso, Alessandro Prelle, Orazio Zanetti, Giulia Lussignoli, Dario Mirabile, Daniele Bellandi, Simona Gentile, Gloria Belotti, Daniele Villani, Taoufiq Harach, Tristan Bolmont, Alessandro Padovani, Marina Boccardi, Giovanni B Frisoni
The pathway leading from amyloid-β deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro- and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients...
August 31, 2016: Neurobiology of Aging
Rong Li, Xiaoxia Yang, Yan Yu, Meilan Zhou, Xiujuan Tian, Shidong Feng, Hanmin Wang
Objective To explore the role of the anti-inflammatory cytokine C1q/tumor necrosis factor related protein 6 (CTRP6) in gentamicin-induced acute kidney injury in rats. Methods SD rats were divided into 5 groups including control group, model group and the other 3 experimental groups. The rats in model group and experimental groups were subcutaneously injected with gentamicin at the dose of 400 mg/(kg.d) for consecutive 2 days to induce acute renal injury. Two days before gentamicin injection, the rats in the 3 experimental groups were given pAd-CTRP6 at the doses of 0...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Jing Qiu, Min Wang, Jun Zhang, Qing Cai, Dan Lu, Yansong Li, Yushu Dong, Tianzhi Zhao, Huisheng Chen
Neuroinflammation remains the primary cause of morbidity and mortality in stroke-induced secondary brain injury. The NOD-like receptor pyrin 3 (NLRP3) inflammasome is involved in diverse inflammatory diseases, including cerebral ischemia, and is thus considered an effective therapeutic target. In the present study, we investigated the neuroprotection of Sinomenine (SINO), a potent natural anti-apoptotic and anti-inflammatory molecule, against cerebral ischemia in a mouse model of middle cerebral artery occlusion (MCAO) in vivo and in an oxygen glucose deprivation (OGD)-treated astrocytes/microglia model in vitro...
October 18, 2016: International Immunopharmacology
Katharina Meier, Stefan K Drexler, Franziska C Eberle, Karine Lefort, Amir S Yazdi
Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an important adaptor protein for inflammasome activation, mediating the secretion of protumorigenic innate cytokines. However, ASC is also known to trigger apoptosis in tumor cells, acting as a tumor-suppressor gene, which is lost in several human cancers. The aim of this study was to evaluate the clinical significance of ASC in human cutaneous squamous cell carcinoma (SCC). Initially, ASC expression was immunohistochemically evaluated in non-metastic and metastatic SCC...
2016: PloS One
Yimin Qiu, Dongmei Chen, Xiaojing Huang, Lina Huang, Liang Tang, Jihong Jiang, Lianhua Chen, Shitong Li
BACKGROUND: Limited surveys have assessed the performance of 5-hydroxytreptamine receptor 1A and its antagonist WAY-100635 in pharmacological manipulations targeting delirium therapies. The purpose of this paper was to assess the central pharmacological activity of WAY-100635 in a rat model of scopolamine-induced delirium and its underlying mechanism. RESULTS: A delirium rat model was established by intraperitoneal injection of scopolamine and behavioral changes evaluated through open field and elevated plus maze experiments...
October 19, 2016: BMC Neuroscience
Chuansheng Guo, Shujun Xie, Zhexu Chi, Jinhua Zhang, Yangyang Liu, Li Zhang, Mingzhu Zheng, Xue Zhang, Dajing Xia, Yuehai Ke, Linrong Lu, Di Wang
No abstract text is available yet for this article.
October 18, 2016: Immunity
Christina J Groß, Olaf Groß
The involvement of the NLRP3 inflammasome in inflammatory diseases has generated interest in identifying endogenous mechanisms that inhibit NLRP3. In this issue of Immunity, Guo et al. (2016) reveal bile acids as negative regulators of the NLRP3 inflammasome.
October 18, 2016: Immunity
Laurie A Dempsey
No abstract text is available yet for this article.
October 19, 2016: Nature Immunology
Feng Zhou, Ying Zhang, Jing Chen, Xuemei Hu, Yancheng Xu
Liraglutide, an effective drug for the treatment of diabetes, has been proven to demonstrate anti-inflammatory and immunomodulatory effects. Hence, this study explored the effects and mechanism of action of liraglutide on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Male BALB/c mice were pre-conditioned with liraglutide or saline prior to intraperitoneal LPS or saline administration. Histopathological examination of lung, the wet/dry (W/D)weight ratio, protein content, inflammatory cell numbers and pro-inflammatory cytokine levels in broncho-alveolar lavage fluid (BAL fluid) were conducted...
October 15, 2016: European Journal of Pharmacology
Rui Kang, Ling Zeng, Yangchun Xie, Zhengwen Yan, Borong Zhou, Lizhi Cao, Daniel J Klionsky, Kevin J Tracey, Jianhua Li, Haichao Wang, Timothy R Billiar, Jianxin Jiang, Daolin Tang
Although the PINK1-PARK2 pathway contributes to the pathogenesis of Parkinson disease, its roles in sepsis (a major challenge for critical care) were previously unknown. Here, we show that pink1(-/-) and park2(-/-) mice are more sensitive to polymicrobial sepsis-induced multiple organ failure and death. The decrease in the circulating level of the neurotransmitter dopamine in pink1(-/-) and park2(-/-) mice accelerates the release of a late sepsis mediator, HMGB1, via HIF1A-dependent anaerobic glycolysis and subsequent NLRP3-dependent inflammasome activation...
October 18, 2016: Autophagy
Diane E Griffin
Measles is an acute systemic viral infection with immune system interactions that play essential roles in multiple stages of infection and disease. Measles virus (MeV) infection does not induce type 1 interferons, but leads to production of cytokines and chemokines associated with nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling and activation of the NACHT, LRR and PYD domains-containing protein (NLRP3) inflammasome. This restricted response allows extensive virus replication and spread during a clinically silent latent period of 10-14 days...
October 12, 2016: Viruses
Christian Adam, Jonas Wohlfarth, Maike Haußmann, Helga Sennefelder, Annette Rodin, Mareike Maler, Stefan F Martin, Matthias Goebeler, Marc Schmidt
Chromium allergy is a common occupational skin disease mediated by chromium (VI)-specific T cells that induce delayed-type hypersensitivity in sensitized individuals. Additionally, chromium (VI) can act as irritant. Both responses critically require innate immune activation, but if and how chromium (VI) elicits this signal is currently unclear.Using human monocytes, primary human keratinocytes and murine dendritic cells we show that chromium (VI) compounds fail to trigger direct proinflammatory activation but potently induce processing and secretion of IL-1β...
October 14, 2016: Journal of Investigative Dermatology
Azadeh Askari, Reza Nosratabadi, Mehdi Khaleghinia, Nahid Zainodini, Derek Kennedy, Ziba Shabani, Mohammad Kazemi Arababadi
Nucleotide-binding domain leucine repeats (NLRs) are required for the recognition of various molecules that are expressed within microbes and are able to actuate appropriate immune responses via activation of cytokines. The current study evaluates the expression levels of NLRP1 and NLRC4, which are components of inflammasomes, in chronic hepatitis B (CHB) virus-infected patients. This study recruited two series of CHB patients (each contained 60 patients) and 60 healthy controls. Real-time polymerase chain reaction (PCR) was employed to evaluate mRNA expression levels of NLRP1, NLRP3, and NLRC4 as well as hepatitis B virus (HBV)-DNA copy number...
October 17, 2016: Viral Immunology
Weijie Chen, Junlian Wang, Yong Luo, Tao Wang, Xiaochun Li, Aiyun Li, Jia Li, Kang Liu, Baolin Liu
BACKGROUND: This study was designed to investigate whether ginsenoside Rb1 (Rb1) and compound K (CK) ameliorated insulin resistance by suppressing endoplasmic reticulum (ER) stress-induced inflammation in adipose tissue. METHODS: To induce ER stress, epididymal adipose tissue from mice or differentiated 3T3 adipocytes were exposed to high glucose. The effects of Rb1 and CK on reactive oxygen species production, ER stress, TXNIP/NLRP3 inflammasome activation, inflammation, insulin signaling activation, and glucose uptake were detected by western blot, emzyme-linked immunosorbent assay, or fluorometry...
October 2016: Journal of Ginseng Research
Ashley A Basiorka, Kathy L McGraw, Erika A Eksioglu, Xianghong Chen, Joseph Johnson, Ling Zhang, Qing Zhang, Brittany A Irvine, Thomas Cluzeau, David A Sallman, Eric Padron, Rami Komrokji, Lubomir Sokol, Rebecca C Coll, Avril A B Robertson, Matthew A Cooper, John L Cleveland, Luke A O'Neill, Sheng Wei, Alan F List
Despite genetic heterogeneity, myelodysplastic syndromes (MDS) share features of cytological dysplasia and ineffective hematopoiesis. We report that a hallmark of MDS is activation of the NLRP3 inflammasome, which drives clonal expansion and pyroptotic cell death. Independent of genotype, MDS hematopoietic stem/progenitor cells (HSPC) overexpress inflammasome proteins and manifest activated NLRP3 complexes that direct activation of caspase-1, generation of IL-1β and IL-18 and pyroptotic cell death. Mechanistically, pyroptosis is triggered by the alarmin S100A9 that is found in excess in MDS HSPC and bone marrow plasma...
October 13, 2016: Blood
Thiago Alves da Costa, Rosária Di Gangi, Rodolfo Thomé, Marina Barreto Felisbino, Amanda Pires Bonfanti, Larissa Lumi Watanabe Ishikawa, Alexandrina Sartori, Eva Burger, Liana Verinaud
T cell maturation takes place within the thymus, a primary lymphoid organ that is commonly targeted during infections. Previous studies showed that acute infection with Paracoccidioides brasiliensis (Pb), the causative agent of paracoccidioidomycosis (PCM), promotes thymic atrophy that is associated with the presence of yeast cells in the organ. However, as human PCM is a chronic infection, it is imperative to investigate the consequences of Pb infection over the thymic structure and function in chronic infection...
2016: PloS One
Laura Schoenlaub, Rama Cherla, Yan Zhang, Guoquan Zhang
Our recent study demonstrated that virulent Coxiella burnetii Nine Mile phase I (NMI) is capable of infecting and replicating within peritoneal B1a cells and that B1a cells play an important role in host defense against C. burnetii infection in mice. However, it remains unknown if avirulent Nine Mile phase II (NMII) can infect and replicate in B1a cells and whether NMI and NMII can differentially interact with B1a cells. In this study, we examined if NMI and NMII can differentially modulate host cell apoptotic signaling in B1a cells...
October 10, 2016: Infection and Immunity
Peipei Zhang, Kohsuke Tsuchiya, Takeshi Kinoshita, Hiroko Kushiyama, Sofya Suidasari, Mizuki Hatakeyama, Hisanori Imura, Norihisa Kato, Takashi Suda
Vitamin B6 includes six water-soluble vitamers: pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN), and their phosphorylated forms. Pyridoxal 5'-phosphate (PLP) is an important cofactor for many metabolic enzymes. Several lines of evidence demonstrate that blood levels of PLP are significantly lower in patients with inflammation than in control subjects, and that vitamin B6 has anti-inflammatory effects, with therapeutic potential for a variety of inflammatory diseases. Although one of our group (NK) previously demonstrated that PL inhibits the NF-κB pathway, the molecular mechanism by which vitamin B6 suppresses inflammation is not well understood...
October 12, 2016: Journal of Biological Chemistry
M B Huante, S Gupta, V C Calderon, S J Koo, M Sinha, B A Luxon, N J Garg, J J Endsley
Pathogens frequently exploit or evade inflammasome activation in order to survive and proliferate. Alternatively, inadequate inflammasome activation by attenuated microorganisms or adjuvanted subunit vaccines may contribute to poor longevity of protection. To further understand these pathways, we determined the differential inflammasome transcriptome of human THP monocyte-derived macrophages in response to Mycobacterium bovis BCG, as compared to LPS or Trypanosoma cruzi. The results identify the highly specific innate recognition programs associated with inflammasome activation by human macrophages exposed to these microbial stimuli...
September 28, 2016: Tuberculosis
Hisa Hui Ling Tseng, Chi Teng Vong, Yiu Wa Kwan, Simon Ming-Yuen Lee, Maggie Pui Man Hoi
Excessive production of reactive oxygen species (ROS) induced by hyperglycemia increased the secretion of interleukin-1β (IL-1β), which contributes to the pathogenesis of diabetes and its complications. Although high glucose (HG)-induced oxidative stress and aberrant Ca(2+) channels activity causes an increase in transmembrane Ca(2+) influx, however the relative contribution of Transient receptor potential (TRP) channels is not well studied. Here, we identified that HG (30 mM glucose for 48 h) induced the activation of the NLRP3-ASC inflammasome, leading to caspase-1 activation, and IL-1β and IL-18 secretion in human monocytic cell lines...
October 12, 2016: Scientific Reports
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