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Cell Free Dna As A Marker Of Training Status In Weightlifters, Jeremy A. Gentles, William G. Hornsby, Christine L. Coniglio, Andy R. Dotterweich, Jon A. Miller, Charles A. Stuart, Michael H. Stone

Jeremy A. Gentles

The purpose of this investigation was to elucidate the changes in cf-DNA as it relates to fluctuations in resistance training workloads and intensities. The relationship between cell free DNA (cf-DNA), C-reactive protein (CRP), creatine kinase (CK), testosterone (T), cortisol (C), testosterone-cortisol ratio (T:C), body mass and body composition were also examined. Eight weightlifters (5 males and 3 females, age = 25 ± 3.5 yr, body mass = 88.3 ± 22.7 kg, height = 173.8 ±8.4 cm) volunteered to participate in this study. Venous blood samples, body mass and body composition were taken six times, each corresponding to the end of …

Cell Free Dna As A Marker Of Training Status In Weightlifters, Jeremy A. Gentles, William G. Hornsby, Christine L. Coniglio, Andy R. Dotterweich, Jon A. Miller, Charles A. Stuart, Michael H. Stone

Andy R. Dotterweich

The purpose of this investigation was to elucidate the changes in cf-DNA as it relates to fluctuations in resistance training workloads and intensities. The relationship between cell free DNA (cf-DNA), C-reactive protein (CRP), creatine kinase (CK), testosterone (T), cortisol (C), testosterone-cortisol ratio (T:C), body mass and body composition were also examined. Eight weightlifters (5 males and 3 females, age = 25 ± 3.5 yr, body mass = 88.3 ± 22.7 kg, height = 173.8 ±8.4 cm) volunteered to participate in this study. Venous blood samples, body mass and body composition were taken six times, each corresponding to the end of …

Exposure To Cerium Oxide Nanoparticles Is Associated With Activation Of Mitogen-Activated Protein Kinases Signaling And Apoptosis In Rat Lungs, Kevin M. Rice, Siva K. Nalabotu, Nandini D.P.K. Manne, Madhukar B. Kolli, Geeta Nandyala, Ravi K. Arvapalli, Jane Y. Ma, Eric R. Blough

Eric Blough

Objectives: With recent advances in nanoparticle manufacturing and applications, potential exposure to nanoparticles in various settings is becoming increasing likely. No investigation has yet been performed to assess whether respiratory tract exposure to cerium oxide (CeO2) nanoparticles is associated with alterations in protein signaling, inflammation, and apoptosis in rat lungs.

Methods: Specific-pathogen-free male Sprague-Dawley rats were instilled with either vehicle (saline) or CeO2 nanoparticles at a dosage of 7.0 mg/kg and euthanized 1, 3, 14, 28, 56, or 90 days after exposure. Lung tissues were collected and evaluated for the expression of proteins associated with inflammation and cellular …

Exposure To Cerium Oxide Nanoparticles Is Associated With Activation Of Mitogen-Activated Protein Kinases Signaling And Apoptosis In Rat Lungs, Kevin M. Rice, Siva K. Nalabotu, Nandini D.P.K. Manne, Madhukar B. Kolli, Geeta Nandyala, Ravi K. Arvapalli, Jane Y. Ma, Eric R. Blough

Ravi K. Arvapalli

Objectives: With recent advances in nanoparticle manufacturing and applications, potential exposure to nanoparticles in various settings is becoming increasing likely. No investigation has yet been performed to assess whether respiratory tract exposure to cerium oxide (CeO2) nanoparticles is associated with alterations in protein signaling, inflammation, and apoptosis in rat lungs.

Methods: Specific-pathogen-free male Sprague-Dawley rats were instilled with either vehicle (saline) or CeO2 nanoparticles at a dosage of 7.0 mg/kg and euthanized 1, 3, 14, 28, 56, or 90 days after exposure. Lung tissues were collected and evaluated for the expression of proteins associated with inflammation and cellular …

Exposure To Cerium Oxide Nanoparticles Is Associated With Activation Of Mitogen-Activated Protein Kinases Signaling And Apoptosis In Rat Lungs, Kevin M. Rice, Siva K. Nalabotu, Nandini D.P.K. Manne, Madhukar B. Kolli, Geeta Nandyala, Ravi K. Arvapalli, Jane Y. Ma, Eric R. Blough

Nandini Manne

Objectives: With recent advances in nanoparticle manufacturing and applications, potential exposure to nanoparticles in various settings is becoming increasing likely. No investigation has yet been performed to assess whether respiratory tract exposure to cerium oxide (CeO2) nanoparticles is associated with alterations in protein signaling, inflammation, and apoptosis in rat lungs.

Methods: Specific-pathogen-free male Sprague-Dawley rats were instilled with either vehicle (saline) or CeO2 nanoparticles at a dosage of 7.0 mg/kg and euthanized 1, 3, 14, 28, 56, or 90 days after exposure. Lung tissues were collected and evaluated for the expression of proteins associated with inflammation and cellular …

Exposure To Cerium Oxide Nanoparticles Is Associated With Activation Of Mitogen-Activated Protein Kinases Signaling And Apoptosis In Rat Lungs, Kevin M. Rice, Siva K. Nalabotu, Nandini D.P.K. Manne, Madhukar B. Kolli, Geeta Nandyala, Ravi K. Arvapalli, Jane Y. Ma, Eric R. Blough

Kevin M Rice

Objectives: With recent advances in nanoparticle manufacturing and applications, potential exposure to nanoparticles in various settings is becoming increasing likely. No investigation has yet been performed to assess whether respiratory tract exposure to cerium oxide (CeO2) nanoparticles is associated with alterations in protein signaling, inflammation, and apoptosis in rat lungs.

Methods: Specific-pathogen-free male Sprague-Dawley rats were instilled with either vehicle (saline) or CeO2 nanoparticles at a dosage of 7.0 mg/kg and euthanized 1, 3, 14, 28, 56, or 90 days after exposure. Lung tissues were collected and evaluated for the expression of proteins associated with inflammation and cellular …

Animal Models Of Rheumatoid Pain: Experimental Systems And Insights., Bradford D Fischer, Adeshina Adeyemo, Michael E O'Leary, Andrea Bottaro

Bradford Fischer

Severe chronic pain is one of the hallmarks and most debilitating manifestations of inflammatory arthritis. It represents a significant problem in the clinical management of patients with common chronic inflammatory joint conditions such as rheumatoid arthritis, psoriatic arthritis and spondyloarthropathies. The functional links between peripheral inflammatory signals and the establishment of the neuroadaptive mechanisms acting in nociceptors and in the central nervous system in the establishment of chronic and neuropathic pain are still poorly understood, representing an area of intense study and translational priority. Several well-established inducible and spontaneous animal models are available to study the onset, progression and chronicization …

Biological Markers For Pulpal Inflammation: A Systematic Review., Dan-Krister Rechenberg, Johnah C. Galicia, Ove A. Peters

Ove Peters

BACKGROUND AND OBJECTIVE: Pulpitis is mainly caused by an opportunistic infection of the pulp space with commensal oral microorganisms. Depending on the state of inflammation, different treatment regimes are currently advocated. Predictable vital pulp therapy depends on accurate determination of the pulpal status that will allow repair to occur. The role of several players of the host response in pulpitis is well documented: cytokines, proteases, inflammatory mediators, growth factors, antimicrobial peptides and others contribute to pulpal defense mechanisms; these factors may serve as biomarkers that indicate the status of the pulp. Therefore, the aim of this systematic review was to …

Functional Local Renin-Angiotensin System In Human And Rat Periodontal Tissue, Carlos Ferreira Santos, Ana Carolina Morandini, Thiago José Dionísio, Flávio A. Faria, Marta C. Lima, Caio M. Figueiredo, Bella L. Colombini-Ishikiriama, Carla Renata Sipert, Rubens P. Maciel, Ana P. Akashi, Gabriela P. Souza, Gustavo P. Garlet, Camila O. Rodini, Sandra L. Amaral, Christiane Becari, Maria C. Salgado, Eduardo B. Oliveira, Isaac Matus, Daniela N. Didier, Andrew S. Greene

Ana Carolina Morandini

The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression …

The Glia Response After Peripheral Nerve Injury: A Comparison Between Schwann Cells And Olfactory Ensheathing Cells And Their Uses For Neural Regenerative Therapies, Matthew J Barton, James St John, Alison Wright, Jenny Ekberg

Jenny Ekberg

The peripheral nervous system (PNS) exhibits a much larger capacity for regeneration than the central nervous system (CNS). One reason for this difference is the difference in glial cell types between the two systems. PNS glia respond rapidly to nerve injury by clearing debris from the injury site, supplying essential growth factors and providing structural support; all of which enhances neuronal regeneration. Thus, transplantation of glial cells from the PNS is a very promising therapy for injuries to both the PNS and the CNS. There are two key types of PNS glia: olfactory ensheathing cells (OECs), which populate the olfactory …

Prophylactic Methylprednisolone To Reduce Inflammation And Improve Outcomes From One Lung Ventilation In Children: A Randomized Clinical Trial., Mary C. Theroux, Alicia Olivant Fisher, Maria E. Rodriguez, Robert P. Brislin, Kirk W. Reichard, Suken A. Shah, Matt Mccoy, Melinda Brown, Kirk W. Dabney, William G. Mackenzie, Douglas A. Katz, Thomas H. Shaffer

Thomas L. Shaffer

BACKGROUND: One lung ventilation (OLV) results in inflammatory and mechanical injury, leading to intraoperative and postoperative complications in children. No interventions have been studied in children to minimize such injury. OBJECTIVE: We hypothesized that a single 2-mg·kg(-1) dose of methylprednisolone given 45-60 min prior to lung collapse would minimize injury from OLV and improve physiological stability. METHODS: Twenty-eight children scheduled to undergo OLV were randomly assigned to receive 2 mg·kg(-1) methylprednisolone (MP) or normal saline (placebo group) prior to OLV. Anesthetic management was standardized, and data were collected for physiological stability (bronchospasm, respiratory resistance, and compliance). Plasma was assayed for …

Effects Of Olanzapine On The Elevation Of Macrophage Infiltration And Pro-Inflammatory Cytokine Expression In Female Rats, Qingsheng Zhang, Meng He, Chao Deng, Hongqin Wang, Xu-Feng Huang

Xu-Feng Huang

The metabolic side-effects of olanzapine have undermined drug compliance and increased concern for this otherwise-effective treatment for schizophrenia. As obesity and type 2 diabetes are associated with low-grade inflammation, and olanzapine-induced weight gain has three typical stages, the current study investigated the inflammatory effects of olanzapine in three treatment stages. Female Sprague-Dawley rats were treated orally with olanzapine (1 mg/kg three times daily) or vehicle for one week, two weeks, and five weeks. Olanzapine significantly increased body weight and white visceral fat deposition in all three treatment stages compared to control. Olanzapine enhanced average adipocyte size and level of macrophage …

Treatment Of Obesity: Weight Loss And Bariatric Surgery, Bruce M. Wolfe, Elizaveta Walker, Robert H. Eckel

Elizaveta Walker

Adiposity Is Associated With Early Reduction In Bone Mass In Pediatric Inflammatory Bowel Disease, Nithya Setty-Shah, Louise S. Maranda, Benjamin U. Nwosu

Benjamin U. Nwosu

Background: The effect of adiposity on bone mass in the early phases of inflammatory bowel disease (IBD) in children and adolescents is unclear.

Aims: To determine the role of adiposity on bone mass in the first 3 years of diagnosis of IBD.

Hypothesis: Increased adiposity will be associated with increased bone mass in both the controls and IBD subjects.

Setting: University tertiary institution.

Methods: Height-adjusted bone mineral density (BMD) z-scores of 25 subjects, age 13.97 ± 2.70y, diagnosed with IBD for < 4 years were compared to 24 controls, age 13.65 ± 2.60y. Overweight was defined as BMI of ≥85^th but <95^th percentile, and obesity as BMI ≥95^thpercentile. Severity of IBD was determined by the Pediatric …

Serum Zinc Concentration And C-Reactive Protein In Individuals With Human Immunodeficiency Virus Infection: The Positive Living With Hiv (Polh) Study (Biological Trace Element Research), Krishna Poudel, Elizabeth Bertone-Johnson, Kalpana Poudel-Tandukar

Kalpana Poudel-Tandukar

Muscular Strength, Aerobic Capacity, And Adipocytokines In Obese Youth After Resistance Training: A Pilot Study, Sarah Schultz, Rachana Dahiya, Gary Leong, David Rowlands, Andrew Hills, Nuala Byrne

Nuala Byrne

Abstract Background Exercise has shown positive training effects on obesity-related inflammation, however, resistance training has shown mixed results concerning adipocytokine levels. Aims The purpose of thispilot study was to explore the effects of resistance training on blood adipocytokine concentrations in obese youth, with specific examination of the relationship between these biomarkers and improved fitness (i.e., aerobic capacity, muscular strength). Methods Fourteen obese adolescents (16.1 ± 1.6 y; BMI: 32.3 ± 3.9 kg/m2) participated in a 16-week resistance training intervention. Body composition, fasting blood concentrations of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), adiponectin, and leptin were measured pre- and post-training. Aerobic …

Osteopontin: A Bridge Between Bone And The Immune System, Ellen M. Gravallese

Ellen M. Gravallese

The molecular mechanisms underlying the putative role of osteopontin in the chronic inflammatory disease rheumatoid arthritis are unclear. A study in a murine model of arthritis now demonstrates that a specific antibody directed against the exposed osteopontin epitope SLAYGLR is capable of preventing inflammatory cell infiltration in arthritic joints.

Critical Roles For Interleukin 1 And Tumor Necrosis Factor Alpha In Antibody-Induced Arthritis, Hong Ji, Allison Pettit, Koichiro Ohmura, Adriana Ortiz-Lopez, Veronique Duchatelle, Claude Degott, Ellen M. Gravallese, Diane Mathis, Christophe Benoist

Ellen M. Gravallese

In spontaneous inflammatory arthritis of K/BxN T cell receptor transgenic mice, the effector phase of the disease is provoked by binding of immunoglobulins (Igs) to joint surfaces. Inflammatory cytokines are known to be involved in human inflammatory arthritis, in particular rheumatoid arthritis, although, overall, the pathogenetic mechanisms of the human affliction remain unclear. To explore the analogy between the K/BxN model and human patients, we assessed the role and relative importance of inflammatory cytokines in K/BxN joint inflammation by transferring arthritogenic serum into a panel of genetically deficient recipients. Interleukin (IL)-1 proved absolutely necessary. Tumor necrosis factor (TNF)-alpha was also …

Chronic Alcohol-Induced Microrna-155 Contributes To Neuroinflammation In A Tlr4-Dependent Manner In Mice, Dora Lippai, Shashi Bala, Timea Csak, Evelyn A. Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

INTRODUCTION: Alcohol-induced neuroinflammation is mediated by pro-inflammatory cytokines and chemokines including tumor necrosis factor-alpha (TNFalpha), monocyte chemotactic protein-1 (MCP1) and interleukin-1-beta (IL-1beta). Toll-like receptor-4 (TLR4) pathway induced nuclear factor-kappaB (NF-kappaB) activation is involved in the pathogenesis of alcohol-induced neuroinflammation. Inflammation is a highly regulated process. Recent studies suggest that microRNAs (miRNAs) play crucial role in fine tuning gene expression and miR-155 is a major regulator of inflammation in immune cells after TLR stimulation. AIM: To evaluate the role of miR-155 in the pathogenesis of alcohol-induced neuroinflammation. METHODS: Wild type (WT), miR-155- and TLR4-knockout (KO) mice received 5% ethanol-containing or isocaloric …

A Population-Based Dietary Inflammatory Index Predicts Levels Of C-Reactive Protein In The Seasonal Variation Of Blood Cholesterol Study (Seasons), Nitin Shivappa, Susan E. Steck, Thomas G. Hurley, James R. Hussey, Yunsheng Ma, Ira S. Ockene, Fred Tabung, James R. Hebert

Yunsheng Ma

OBJECTIVE: To perform construct validation of the population-based Dietary Inflammatory Index (DII) using dietary data from two different dietary assessments and serum high-sensitivity C-reactive protein (hs-CRP) as the construct validator.

DESIGN: Using data derived from (i) three 24 h dietary recalls (24HR) at baseline and at the end of each subsequent quarter (i.e. up to fifteen over a year) and (ii) a 7 d dietary recall (7DDR) measured at baseline and then quarterly, regression analyses were conducted to test the effect of the DII score on serum hs-CRP as dichotomous (3 mg/l), while controlling for important potential confounders.

SETTING: Existing …

Teasaponin Reduces Inflammation And Central Leptin Resistance In Diet-Induced Obese Male Mice, Yinghua Yu, Yizhen Wu, Alexander Szabo, Zhixiang Wu, Hongqin Wang, Duo Li, Xu-Feng Huang

Yizhen Wu

Chronic inflammation is involved in the pathogenesis of obesity and type 2 diabetes. Recently, teasaponin, an extract from tea, has been shown to have anti-inflammatory effects. We examined the effect of teasaponin on obesity, inflammation, glucose metabolism and central leptin sensitivity, in obese mice fed a high-fat (HF) diet for 16 weeks. Intraperitoneal injections of teasaponin (10mg/kg, daily) for 21 days significantly decreased the food intake and body weight of HF diet-induced obese mice. Teasaponin treatment also reduced the protein levels of pro-inflammatory cytokines (TNF-α, IL-6 and/or IL-1β) and NF-κB signaling (p-IKK and p-IκBα) in adipose tissue and the liver. …

Teasaponin Reduces Inflammation And Central Leptin Resistance In Diet-Induced Obese Male Mice, Yinghua Yu, Yizhen Wu, Alexander Szabo, Zhixiang Wu, Hongqin Wang, Duo Li, Xu-Feng Huang

Yizhen Wu

Chronic inflammation is involved in the pathogenesis of obesity and type 2 diabetes. Recently, teasaponin, an extract from tea, has been shown to have anti-inflammatory effects. We examined the effect of teasaponin on obesity, inflammation, glucose metabolism and central leptin sensitivity, in obese mice fed a high-fat (HF) diet for 16 weeks. Intraperitoneal injections of teasaponin (10mg/kg, daily) for 21 days significantly decreased the food intake and body weight of HF diet-induced obese mice. Teasaponin treatment also reduced the protein levels of pro-inflammatory cytokines (TNF-α, IL-6 and/or IL-1β) and NF-κB signaling (p-IKK and p-IκBα) in adipose tissue and the liver. …

House Finch Populations Differ In Early Inflammatory Signaling And Pathogen Tolerance At The Peak Of Mycoplasma Gallisepticum Infection, James S. Adelman, Laila Kirkpatrick, Jessica L. Grodio, Dana M. Hawley

James S. Adelman

Host individuals and populations often vary in their responses to infection, with direct consequences for pathogen spread and evolution. While considerable work has focused on the mechanisms underlying differences in resistance—the ability to kill pathogens— we know little about the mechanisms underlying tolerance— the ability to minimize fitness losses per unit pathogen. Here, we examine patterns and mechanisms of tolerance between two populations of house finches (Haemorhous [formerly Carpodacus] mexicanus) with different histories with the bacterial pathogen Mycoplasma gallisepticum (MG). After infection in a common environment, we assessed two metrics of pathology, mass loss and eye lesion severity, as proxies …

Controlling Viral Immuno-Inflammatory Lesions By Modulating Aryl Hydrocarbon Receptor Signaling, Tamara Veiga-Parga, A Suryawanshi, B T. Rouse

Tamara Veiga-Parga

Ocular herpes simplex virus infection can cause a blinding CD4+ T cell orchestrated immuno-inflammatory lesion in the cornea called Stromal Keratitis (SK). A key to controlling the severity of SK lesions is to suppress the activity of T cells that orchestrate lesions and enhance the representation of regulatory cells that inhibit effector cell function. In this report we show that a single administration of TCDD (2, 3, 7, 8- Tetrachlorodibenzo-p-dioxin), a non-physiological ligand for the AhR receptor, was an effective means of reducing the severity of SK lesions. It acted by causing apoptosis of Foxp3- CD4+ T cells but had …

Effects Of Canola And Corn Oil Mimetic On Jurkat Cells, Gabriela Ion, Kayla Fazio, Juliana A. Akinsete, W. Elaine Hardman

Gabriela Ion

BACKGROUND: The Western diet is high in omega-6 fatty acids and low in omega-3 fatty acids. Canola oil contains a healthier omega 3 to omega 6 ratio than corn oil. Jurkat T leukemia cells were treated with free fatty acids mixtures in ratios mimicking that found in commercially available canola oil (7% α-linolenic, 30% linoleic, 54% oleic) or corn oil (59% linoleic, 24% oleic) to determine the cell survival or cell death and changes in expression levels of inflammatory cytokines and receptors following oil treatment. METHODS: Fatty acid uptake was assessed by gas chromatography. Cell survival and cell death were …

Effects Of Canola And Corn Oil Mimetic On Jurkat Cells, Gabriela Ion, Kayla Fazio, Juliana A. Akinsete, W. Elaine Hardman

Elaine Hardman Ph.D.

BACKGROUND: The Western diet is high in omega-6 fatty acids and low in omega-3 fatty acids. Canola oil contains a healthier omega 3 to omega 6 ratio than corn oil. Jurkat T leukemia cells were treated with free fatty acids mixtures in ratios mimicking that found in commercially available canola oil (7% α-linolenic, 30% linoleic, 54% oleic) or corn oil (59% linoleic, 24% oleic) to determine the cell survival or cell death and changes in expression levels of inflammatory cytokines and receptors following oil treatment. METHODS: Fatty acid uptake was assessed by gas chromatography. Cell survival and cell death were …

Residential Traffic Exposure, Pulse Pressure, And C-Reactive Protein: Consistency And Contrast Among Exposure Characterization Methods, Christine L. Rioux, Katherine L. Tucker, Mkaya Mwamburi, David M. Gute, Steven A. Cohen, Doug Brugge

Katherine L. Tucker

Background: Traffic exposure may increase cardiovascular disease (CVD) risk via systemic inflammation and elevated blood pressure, two important clinical markers for managing disease progression. Objectives: We assessed degree and consistency of association between traffic exposure indicators as predictors of C-reactive protein (CRP) and pulse pressure (PP) in an adult U.S. Puerto Rican population (n = 1,017). Methods: Cross-sectional information on health and demographics and blood data was collected. Using multiple linear regression, we tested for associations between CRP, PP, and six traffic exposure indicators including residential proximity to roads with > 20,000 vehicles/day and traffic density [vehicle miles traveled per square …

The Inflammatory And Normal Transcriptome Of Mouse Bladder Detrusor And Mucosa, Marcia R. Saban, Helen L. Hellmich, Mary Turner, Ngoc-Bich Nguyen, Rajanikanth Vadigepalli, David W. Dyer, Robert E. Hurst, Michael Centola, Ricardo Saban

Rajanikanth Vadigepalli

Background An organ such as the bladder consists of complex, interacting set of tissues and cells. Inflammation has been implicated in every major disease of the bladder, including cancer, interstitial cystitis, and infection. However, scanty is the information about individual detrusor and urothelium transcriptomes in response to inflammation. Here, we used suppression subtractive hybridizations (SSH) to determine bladder tissue- and disease-specific genes and transcriptional regulatory elements (TRE)s. Unique TREs and genes were assembled into putative networks. Results It was found that the control bladder mucosa presented regulatory elements driving genes such as myosin light chain phosphatase and calponin 1 that …

Identification And Characterization Of Kava-Derived Compounds Mediating Tnf-Α Suppression, Michael P. Pollastri, Adrian Whitty, Jamie Cassidy Merrill, Trent D. Ashton, Salomon Amar

Michael Pollastri

There is a substantial unmet need for new classes of drugs that block TNF-α-mediated inflammation, and particularly for small molecule agents that can be taken orally. We have screened a library of natural products against an assay measuring TNF-α secretion in lipopolysaccharide (LPS)-stimulated THP-1 cells, seeking compounds capable of interfering with the TNF-α inducing transcription factor Lipopolysaccharide Induced TNF Alpha Factor (LITAF). Among the active compounds were several produced by the kava plant (Piper mysticum), extracts of which have previously been linked to a range of therapeutic effects. When tested in vivo, a representative of these compounds, kavain, was found …

Myd88-Dependent Il-1 Receptor Signaling Is Essential For Gouty Inflammation Stimulated By Monosodium Urate Crystals, Chun-Jen Chen, Yan Shi, Arron Hearn, Katherine A. Fitzgerald, Douglas T. Golenbock, George W. Reed, Shizuo Akira, Kenneth L. Rock

Katherine A. Fitzgerald

While it is known that monosodium urate (MSU) crystals cause the disease gout, the mechanism by which these crystals stimulate this inflammatory condition has not been clear. Here we find that the Toll/IL-1R (TIR) signal transduction adaptor myeloid differentiation primary response protein 88 (MyD88) is required for acute gouty inflammation. In contrast, other TIR adaptor molecules, TIRAP/Mal, TRIF, and TRAM, are not required for this process. The MyD88-dependent TLR1, -2, -4, -6, -7, -9, and -11 and IL-18 receptor (IL-18R) are not essential for MSU-induced inflammation. Moreover, MSU does not stimulate HEK cells expressing TLR1-11 to activate NF-kappaB. In contrast, …