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Stephan Brauckmann, Katharina Effenberger-Neidnicht, Herbert de Groot, Michael Nagel, Christian Mayer, Jürgen Peters, Matthias Hartmann
While hemolysis in patients with sepsis is associated with increased mortality its mechanisms are unknown and Toll-like receptor (TLR)-4 mediated effects, complement-mediated hemolysis, or direct cell membrane effects are all conceivable mechanisms. In this study, we tested the hypotheses that toxic lipopolysaccharide (LPS) as well as non-toxic RS-LPS evokes hemolysis (1) by direct membrane effects, and (2) independent of the complement system and TLR-4 activation. We found, that incubation with LPS resulted in a marked time and concentration dependent increase of free hemoglobin concentration and LDH activity in whole blood and washed red cells...
October 19, 2016: Scientific Reports
Haleh Vaez, Moslem Najafi, Maryam Rameshrad, Negisa Seyed Toutounchi, Mehraveh Garjani, Jaleh Barar, Alireza Garjani
Toll like receptors (TLRs) are key players in the innate immune responses. The energy sensing enzyme, AMPK, has been implicated in the modulation of immunity. The present study investigated whether AMPK activation by metformin could contribute to the regulation of immune responses in the isolated heart via suppression of TLR4 activity, independent of circulatory immunity. Isolated Wistar rat hearts were perfused with Krebs-Henseleit buffer in the absence or presence of lipopolysaccharide (LPS; 0.2μM), LPS+metformin (10mM), and LPS+metformin+compound C (10μM)...
October 14, 2016: International Immunopharmacology
X M Chen, F Q Li, S Yan, X C Wu, C L Tang
OBJECTIVE: To investigate the anti-inflammation effects by activation of the cholinergic anti-inflammatory pathway and its mechanisms in non-alcoholic steatohepatitis (NASH) model mice. METHODS: 6-week-old male C57BL/6J (B6) mice were randomly divided into four groups: the first group was normal mice, injected with saline; the second group was normal mice, injected with nicotine; the third group was NASH model mice, injected with saline; the fourth group was NASH model mice, injected with nicotine...
October 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Lucas Pires Garcia Oliveira, Fernanda Lopes Conte, Eliza de Oliveira Cardoso, Bruno José Conti, Karina Basso Santiago, Marjorie de Assis Golim, Maria Teresa Cruz, José Maurício Sforcin
OBJECTIVES: Geopropolis (GEO) in combination with doxorubicin (DOX) reduced HEp-2 cells viability compared to GEO and DOX alone. A possible effect of this combination on the innate immunity could take place, and its effects were analysed on THP-1 cell - a human leukaemia monocytic cell line used as a model to study monocyte activity and macrophage activity, assessing cell viability, expression of cell markers and cytokine production. METHODS: THP-1 cells were incubated with GEO, DOX and their combination...
October 17, 2016: Journal of Pharmacy and Pharmacology
Daiki Yamanaka, Takashi Kawano, Atsushi Nishigaki, Bun Aoyama, Hiroki Tateiwa, Marie Shigematsu-Locatelli, Fabricio M Locatelli, Masataka Yokoyama
PURPOSE: In the present study, we examined whether and by what mechanisms dexmedetomidine (DMED) prevents the development of systemic inflammation (SI)-induced cognitive dysfunction in aged rats. METHODS: Animals received a single intraperitoneal (i.p.) injection of either 5.0 mg/kg lipopolysaccharide (LPS) or vehicle. LPS-treated rats were further divided into three groups: early DMED, late DMED, or midazolam (MDZ) treatment (n = 12 each). Seven days after LPS injection, cognitive function was evaluated using a novel object recognition task, followed by measurement of hippocampal levels of proinflammatory cytokines and Toll-like receptor 4 (TLR-4) expression...
October 13, 2016: Journal of Anesthesia
Zemin Li, Xiaolin Wang, Hehai Pan, Hao Yang, Xiang Li, Kuibo Zhang, Hua Wang, Zhaomin Zheng, Hui Liu, Jianru Wang
OBJECTIVE: This study was to investigate whether resistin induces the expression of CCL4 during IVDD and whether Toll-like receptor-4 (TLR-4) and the NF-κB signaling pathway are involved in this process. METHODS: The expression pattern of resistin and CCL4 in different degenerated human NP tissues were measured by qPCR; Effect of resistin on the migration of macrophages was measured by cell migration assay. Resistin-induced CCL4 expression were analyzed by qPCR, ELISA and cell immunofluorescence...
October 10, 2016: Osteoarthritis and Cartilage
Nargis Khan, Susanta Pahari, Aurobind Vidyarthi, Mohammad Aqdas, Javed N Agrewala
Tuberculosis (TB) is the leading cause of morbidity and mortality among all infectious diseases. Failure of Bacillus Calmette Guerin as a vaccine and serious side-effects and toxicity due to long-term TB drug regime are the major hurdles associated with TB control. The problem is further compounded by the emergence of drug-resistance strains of Mycobacterium tuberculosis (Mtb). Consequently, it demands a serious attempt to explore safer and superior treatment approaches. Recently, an improved understanding of host-pathogen interaction has opened up new avenues for immunotherapy for treating TB...
2016: Frontiers in Immunology
Li-Xue Zhao, Jun-Rong Du, Hong-Jing Zhou, Dong-Ling Liu, Man-Xia Gu, Fang-Yi Long
BACKGROUND: Peroxiredoxins (Prxs) are proposed to function as damage-associated molecular patterns (DAMPs) and contribute to post-ischemic neuroinflammation and brain injury by activating Toll-like receptor (TLR) 4 at the acute and subacute phases after ischemic stroke. However, there are few studies concerning the inflammatory profiles of six distinct subtypes of Prxs (Prx1-Prx6). Our previous study demonstrated that the protective effect of ligustilide (LIG) against cerebral ischemia was associated with inhibition of neuroinflammatory response and Prx/TLR4 signaling in rats...
2016: PloS One
Bruno J Conti, Karina B Santiago, Eliza O Cardoso, Paula P Freire, Robson F Carvalho, Marjorie A Golim, José M Sforcin
OBJECTIVES: Dendritic cells (DCs) are antigen-presenting cells, essential for recognition and presentation of pathogens to T cells. Propolis, a resinous material produced by bees from various plants, exhibits numerous biological properties, highlighting its immunomodulatory action. Here, we assayed the effects of propolis on the maturation and function of human DCs. METHODS: DCs were generated from human monocytes and incubated with propolis and LPS. NF-κB and cytokines production were determined by ELISA...
October 7, 2016: Journal of Pharmacy and Pharmacology
Werner Schmid, Gottfried Novacek, Harald Vogelsang, Pavol Papay, Christian Primas, Alexander Eser, Simon Panzer
Platelets are activated in Crohn's disease (CD) and interplay with leukocytes. Engagement of Toll-like receptor-4 (TLR-4), which is expressed in human platelets, may be involved in crosstalks between platelets and leukocytes leading to their mutual activation for host defense. Human neutrophil peptides (HNPs), lipoprotein binding peptides, and sCD14 were determined by enzyme-linked immunosorbent assays in 42 patients with active CD, in 43 patients with CD in remission, and in 30 healthy individuals. Neutrophil-platelet aggregates and binding of the TLR-4 monoclonal antibody to platelets were determined by flow cytometry...
October 7, 2016: European Journal of Clinical Investigation
Emmanuel Monnet, Geneviève Lapeyre, Eveline van Poelgeest, Philippe Jacqmin, Kathy de Graaf, Joannes Reijers, Matthijs Moerland, Jacobus Burggraaf, Cristina de Min
Toll-like receptor (TLR) 4 pathways are major contributors to pathological inflammatory responses induced by tissue damage. NI-0101 is the first monoclonal antibody blocking TLR4 signaling. This activity is independent of the ligand type and concentration, therefore blocking potentially any TLR4 ligands. A Phase 1 single ascending dose study was conducted in 73 healthy volunteers (HV) to evaluate NI-0101 tolerability, preliminary safety, pharmacokinetics and pharmacodynamics, in absence and in presence of a systemic challenge with lipopolysaccharide (LPS), a TLR4 ligand...
October 5, 2016: Clinical Pharmacology and Therapeutics
Gihan G Moustafa, Mohamed M A Hussein
The efficacy of aged garlic extract (AGE) in alleviating the hepatic inflammation and pulmonary fibrotic responses induced by titanium dioxide (TiO2) toxicity was studied. The control group received distilled water. AGE-treated group received AGE (2ml/kgbw). TiO2- intoxicated group received TiO2 (5g/kgbw). AGE combined with TiO2 treated group administered AGE prior TiO2 by six hours at the same previously doses. All treatments were given orally every other day for two months. TiO2- intoxicated rats elicited a significant up-regulation in hepatic TLR-2, TLR-4, NF-ĸB/p65, CYP1B1 and CYP2B1 with pulmonary MMP-9, TIMP-1, TGF-β1, collagen-1α, fibronectin mRNA...
October 1, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yuriko Itzel Sánchez-Zamora, Imelda Juarez-Avelar, Alicia Vazquez-Mendoza, Marcia Hiriart, Miriam Rodriguez-Sosa
Macrophage migration inhibitory factor (Mif) is highly expressed in type 1 diabetes mellitus (T1DM). However, there is limited information about how Mif influences the activation of macrophages (Mφ) and dendritic cells (DC) in T1DM. To address this issue, we induced T1DM by administering multiple low doses of streptozotocin (STZ) to Mif-/- or wild-type (Wt) BALB/c mice. We found that Mif-/- mice treated with STZ (Mif-/-STZ) developed lower levels of hyperglycemia, inflammatory cytokines, and specific pancreatic islet antigen- (PIAg-) IgG and displayed reduced cellular infiltration into the pancreatic islets compared to Wt mice treated with STZ (WtSTZ)...
2016: Journal of Diabetes Research
Hongbin Jia, Shuangshuang Xu, Qingzhen Liu, Jian Liu, Jianguo Xu, Weiyan Li, Yi Jin, Qing Ji
The molecular mechanisms underlying neuropathic pain have yet to be elucidated. The present study aimed to examine the modulation of neuroimmune activation in the spinal cord by the synthetic peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, pioglitazone (Pio), in a rat model of neuropathic pain induced by chronic constriction injury (CCI). Rats were randomly assigned into four groups: Sham surgery with vehicle, chronic constriction injury with vehicle or Pio (10 mg/kg), and chronic constriction injury with Pio and a PPAR-γ antagonist GW9662 (2 mg/kg)...
October 2016: Experimental and Therapeutic Medicine
Nancy Gupta, Satish Vedi, Dennis Y Kunimoto, Babita Agrawal, Rakesh Kumar
Mycobacterium tuberculosis (Mtb), the bacterial cause of tuberculosis, is a leading infectious agent worldwide. The development of a new vaccine against Mtb is essential to control global spread of tuberculosis, since the current vaccine BCG is not very effective and antibiotic resistance is a serious, burgeoning problem. ESAT-6 is a secreted protein of Mtb, which is absent in BCG but has been implicated in inducing protective immunity against Mtb. Peptide based subunit vaccines are attractive due to their safety and high specificity in eliciting immune responses, but small synthetic peptides are usually not very immunogenic...
September 29, 2016: Vaccine
Sara Montserrat-Sangrà, Lorena Alborch, Laura Ordeix, Laia Solano-Gallego
Innate immunity, in particular, the role of toll-like receptors (TLRs), has not been extensively studied in canine L. infantum infection. The main aim of this study was to determine the transcription of TLR2 and TLR4 in the blood of dogs with natural clinical leishmaniosis at the time of diagnosis and during treatment follow-up and subsequently correlate these findings with clinical, serological and parasitological data. Forty-six Leishmania-seropositive sick dogs with a high antibody level at the time of diagnosis were studied and compared with 34 healthy seronegative dogs...
September 15, 2016: Veterinary Parasitology
Jonathan Laiño, Julio Villena, Paulraj Kanmani, Haruki Kitazawa
Researchers have demonstrated that lactic acid bacteria (LAB) with immunomodulatory capabilities (immunobiotics) exert their beneficial effects through several molecules, including cell wall, peptidoglycan, and exopolysaccharides (EPS), that are able to interact with specific host cell receptors. EPS from LAB show a wide heterogeneity in its composition, meaning that biological properties depend on the strain and. therefore, only a part of the mechanism of action has been elucidated for these molecules. In this review, we summarize the current knowledge of the health-promoting actions of EPS from LAB with special focus on their immunoregulatory actions...
August 15, 2016: Microorganisms
Sardar Sindhu, Nadeem Akhter, Steve Shenouda, Ajit Wilson, Rasheed Ahmad
BACKGROUND: Fetuin-A/AHSH is a novel hepatokine that acts as a vascular calcification inhibitor and as an endogenous TLR-4 ligand. Fetuin-A may act as a positive or negative acute phase protein (APP) in disease conditions. The relationship between circulatory fetuin-A and inflammatory biomarkers in type-2 diabetes (T2D) remains controversial. Therefore, the purpose of this study was to determine the plasma fetuin-A levels in 53 T2D (BMI = 29.7 ± 4.5 kg/m(2)) and 72 non-diabetic individuals (BMI = 28...
September 26, 2016: BMC Immunology
Ewelina Grywalska, Anna Hymos, Izabela Korona-Głowniak, Marcin Pasiarski, Agnieszka Stelmach-Gołdyś, Stanisław Góźdź, Anna Malm, Jacek Rolinski
INTRODUCTION: Since 2012, both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23) have been recommended for pneumococcal infection prevention in patients with chronic lymphocytic leukemia (CLL). Available literature data indicate that leukemic cells may respond to the presence of pathogens through specific Toll-like receptors (TLR). OBJECTIVES: The aim of the study was to assess the effect of in vitro PPV23 stimulation of peripheral blood mononuclear cells (PBMCs) on expression of TLR-2, TLR-4, CD25, CD69, and CD95 on the surface of CD3+ T cells and CD19+ B cells in CLL patients...
2016: Postȩpy Higieny i Medycyny Doświadczalnej
Gopu Sriram, Vaishali Prakash Natu, Intekhab Islam, Xin Fu, Chaminda Jayampath Seneviratne, Kai Soo Tan, Tong Cao
Periodontitis involves complex interplay of bacteria and host immune response resulting in destruction of supporting tissues of the tooth. Toll-like receptors (TLRs) play a role in recognizing microbial pathogens and eliciting an innate immune response. Recently, the potential application of multipotent stem cells and pluripotent stem cells including human embryonic stem cells (hESCs) in periodontal regenerative therapy has been proposed. However, little is known about the impact of periodontopathogens on hESC-derived progenies...
2016: Stem Cells International
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