Digital Commons Network^™

Leptospiral Hemolysins Induce Proinflammatory Cytokines Through Toll-Like Receptor 2-And 4-Mediated Jnk And Nf-Κb Signaling Pathways, Huan Wang, Yifei Hu, David M. Ojcius, X. Frank Yang, Chenglin Zhang, Shibiao Ding, Xu'ai Lin, Jie Yan

All Dugoni School of Dentistry Faculty Articles

Infection with pathogenic Leptospira species causes serious systemic inflammation in patients. Although a few leptospiral proinflammatory molecules have been identified, Leptospira likely encodes other unidentified strong inflammation stimulators. The pathogenic L. interrogans genome encodes numerous putative hemolysin genes. Since hemolysins from other bacteria can cause inflammatory reactions, we hypothesized that leptospiral hemolysins may function as proinflammatory stimulators that contribute to the strong inflammation associated with Leptospira infection.

Melanopsin Mediates Retrograde Visual Signaling In The Retina, Dao-Qi Zhang, Michael A. Belenky, Patricia J. Sollars, Gary E. Pickard, Douglas G. Mcmahon

School of Veterinary and Biomedical Sciences: Faculty Publications

The canonical flow of visual signals proceeds from outer to inner retina (photoreceptors→bipolar cells→ganglion cells). However, melanopsin-expressing ganglion cells are photosensitive and functional sustained light signaling to retinal dopaminergic interneurons persists in the absence of rods and cones. Here we show that the sustained-type light response of retinal dopamine neurons requires melanopsin and that the response is mediated by AMPA-type glutamate receptors, defining a retrograde retinal visual signaling pathway that fully reverses the usual flow of light signals in retinal circuits.

Regulation Of To Xin Synthesis By Clostridium Difficile, Charles Darkoh

Dissertations and Theses (Open Access)

Clostridium difficile is the leading definable cause of nosocomial diarrhea worldwide due to its virulence, multi-drug resistance, spore-forming ability, and environmental persistence. The incidence of C. difficile infection (CDI) has been increasing exponentially in the last decade. Virulent strains of C. difficile produce either toxin A and/or toxin B, which are essential for the pathogenesis of this bacterium. Current methods for diagnosing CDI are mostly qualitative tests that detect the bacterium, the toxins, or the toxin genes. These methods do not differentiate virulent C. difficile strains that produce active toxins from non-virulent strains that do not produce toxins or produce …

Inhibition Of Burkholderia Multivorans Adhesion To Lung Epithelial Cells By Bivalent Lactosides, Ciara Wight, Rosaria Leyden, Paul V. Murphy, Máire Callaghan, Trinidad Velasco-Torrijos, Siobhan Mcclean

Articles

Burkholderia cepacia complex (Bcc) is an opportunistic pathogen in cystic fibrosis patients which is inherently resistant to antimicrobial agents. The mechanisms of attachment and pathogenesis of Bcc, a group of 17 species, are poorly understood. The most commonly identified Bcc species in newly colonised patients, Burkholderia multivorans, continues to be acquired from the environment. Development of therapies which can prevent or reduce the risk of colonization on exposure to Bcc in the environment would be a better alternative to antimicrobial agents. Previously, it has been shown that Bcc strains bound to many glycolipid receptors on lung epithelia. Using a …

The Anti-Tumorigenic Mushroom Agaricus Blazei Murill Enhances Il-1Β Production And Activates The Nlrp3 Inflammasome In Human Macrophages, Tsung-Teng Huang, David M. Ojcius, John Ding-E. Young, Yi-Hui Wu, Yun-Fei Ko, Tsui-Yin Wong, Cheng-Yeu Wu, Chia-Chen Lu, Hsin-Chih Lai

All Dugoni School of Dentistry Faculty Articles

Agaricus blazei Murill (AbM) has been reported to possess immune activity against tumors and infections through stimulation of mononuclear phagocytes. Recently, AbM extract was shown to induce the production of the pro-inflammatory cytokine, interleukin-1β (IL-1β), in human monocytes. IL-1β is a key pro-inflammatory cytokine produced by activated macrophages and monocytes and its secretion is strictly controlled by the inflammasome. The purpose of this study is to investigate the effect of AbM water extracts on the regulation of IL-1β production and activation of the NLRP3 inflammasome in human THP-1 macrophages. The NLRP3 inflammasome consists of an NLRP3 receptor, an adaptor protein …

Caehnorhabditis Elegans: A Low-Cost In Vivo Animal Model For Efficacy Studies Of Novel Antibiotics, Rylee Ann Gregory

Undergraduate Honors Capstone Projects

Since the 1940s, antibiotics have greatly reduced the adverse effects of infectious diseases caused by microbes. However, due to excessive, and often incorrect, use of known antibiotics, many organisms have adapted antibiotic resistance. Currently, over 70% of known infectious bacteria are resistant to at least one antibiotic. In the U.S. , 90,000 deaths occur each year due to infection by bacteria resistant to antibiotics. This number has increased by nearly 75,000 in the last 20 years. It is necessary, therefore, to continue developing new antibiotics in an effort to keep up with increasing antibiotic resistance. Traditional in vitro and whole …

Host Pathogen Interactions: Is Arabidopsis Thaliana Remembered By Its Nemesis Pseudomonas Syringae?, Daniel Z. Kreiser

Lawrence University Honors Projects

Plants contain innate immune systems that deter pathogen infection. Pattern recognition receptors bind microbe-associated molecular patterns (MAMPs), triggering immunity. MAMPs are proteins exclusive to pathogens that are typically indispensable for their survival. For this reason, MAMPs cannot be mutated or removed without causing pathogen death. However, this does not necessitate constitutive expression of MAMPs. In this study, the MAMP response of Arabidopsis thaliana was utilized to determine differential detection of MAMPs expressed by Pseudomonas syringe pv. tomato DC3000 when pretreated with A. thaliana. Results demonstrated that more MAMPs are detected when P. syringae had previously encountered A. thaliana, …

Synthesis Of S-Ribosyl-L-Homocysteine And Analogs Modified At The Homocysteine-C3 Position, Ruoyi Liu

Master's Theses

Quorum sensing (QS) is a process of bacterial cell-to-cell communication that conveys population density information in order to coordinate gene expression to produce synchronized behaviors. QS regulates the expression of virulence genes in many species of bacteria; hence, the manipulation of QS pathways may lead to treatment options against many bacterial diseases. The LuxS enzyme converts S-ribosyl-L-homocysteine (SRH) into homocysteine (HCys) and 4(S),5-dihydroxypentane-2,3-dione (DPD), which is the precursor of autoinducer-2 (AI-2). Thus, inhibitors of LuxS could prevent QS by halting the conversion of SRH to AI-2 rendering the cell “uncommunicative”. This work shows the successful chemical synthesis …

Determination Of Selectivity And Potential For Drug Resistance Of Novel Antimalarial Compounds From Nature-Inspired Synthetic Libraries, Eric Keasler

HIM 1990-2015

As malaria, caused by Plasmodium spp., continues to afflict millions of people worldwide, there is a dire need for the discovery of novel, inexpensive antimalarial drugs. Although there are effective drugs on the market, the consistent development of drug resistant species has decreased their efficacy, further emphasizing that novel therapeutic measures are urgently needed. Natural products provide the most diverse reservoir for the discovery of unique chemical scaffolds with the potential to effectively combat malarial infections, but, due to their complex structures, they often pose extreme challenges to medicinal chemists during pharmacokinetic optimization. In our laboratory we have performed unbiased, …

A Leishmania Mitogen Activated Protein Kinase As A Potential Anti-Parasitic Drug Target : Purification, Characterization And Inhibitor Interactions, Aysenur Sayakci

Theses, Dissertations and Culminating Projects

The disease, Leishmaniasis, is caused by the protozoal parasite Leishmania, which is transmitted by the bite of an infected Phlebotomine female sandfly. It is a significant health problem in tropical regions of the world and new therapeutic approaches for treating this disease are urgently needed.

Protozoal MAPKs (Mitogen Activated Protein Kinases) play important roles in parasite viability and infectivity and as such, represent viable drug targets. It has been demonstrated that LmxMPKl is an essential MAPK required for the parasite to establish infection and for proliferation of the amastigote stage (the mammalian stage of the parasite) of the parasite. In …

An Investigation Of Trypanosoma Brucei Hexokinases: Localization, Oligomerization, And Inhibition, April Joice

All Dissertations

Trypanosoma brucei is the causative agent of African sleeping sickness in humans and nagana in livestock. The parasite inhabits multiple environmental niches including the bloodstream of the mammalian host and the mid-gut of the tsetse fly vector. While in the bloodstream of its mammalian host, the organism depends solely on glycolysis for production of ATP. My studies focus on the first enzyme in glycolysis, hexokinase.
T. brucei has two hexokinases, TbHK1 and TbHK2 that are 98.5% identical at the nucleotide level. The hexokinases are expressed in the glycosomes of both procyclic form and bloodstream form parasites. Glycosomes are peroxisome-like organelles …

Interaction Of Environmental B. Cenocepacia Strains With Cystic Fibrosis And Non-Cystic Fibrosis Bronchial Epithelial Cells In Vitro., Annamaria Bevivino, Luisa Pirone, Ruth Pilkington, Noemi Cifani, Claudia Dalmastri, Máire Callaghan, Fiorentina Ascenzioni, Siobhan Mcclean

Articles

Burkholderia cenocepacia is an important human pathogen in patients with cystic fibrosis (CF). Non-clinical reservoirs may play a role in the acquisition of infections, so it is important to evaluate the pathogenic potential of environmental B. cenocepacia isolates. In this study, we investigated the interactions of two environmental B. cenocepacia strains (Mex1 and MCII-168) with two bronchial epithelial cell lines,16HBE14o- and CFBE41o-, which have a non-CF and a CF phenotype, respectively.

The environmental strains showed a significantly lower level of invasion into both CF- and non-CF cells in comparison with the clinical B. cenocepacia LMG16656^T strain. Exposure of polarized …

Development Stage-Specific Proteomic Profiling Uncovers Small, Lineage Specific Proteins Most Abundant In The Aspergillus Fumigatus Conidial Proteome, Moo-Jin Suh, Natalie D. Fedorova, Steven E. Cagas, Susan Hastings, Robert D. Fleischmann, Scott N. Peterson, David S. Perlin, William C. Nierman, Rembert Pieper, Michelle Momany

Biochemistry and Molecular Medicine Faculty Publications

Background

The pathogenic mold Aspergillus fumigatus is the most frequent infectious cause of death in severely immunocompromised individuals such as leukemia and bone marrow transplant patients. Germination of inhaled conidia (asexual spores) in the host is critical for the initiation of infection, but little is known about the underlying mechanisms of this process.

Results

To gain insights into early germination events and facilitate the identification of potential stage-specific biomarkers and vaccine candidates, we have used quantitative shotgun proteomics to elucidate patterns of protein abundance changes during early fungal development. Four different stages were examined: dormant conidia, isotropically expanding conidia, hyphae …

Activation Of An Nlrp3 Inflammasome Restricts Mycobacterium Kansasii Infection, Chang-Chieh Chen, Sheng-Hui Tsai, Chia-Chen Lu, Shiau-Ting Hu, Ting-Shu Wu, Tsung-Teng Huang, Najwane Saïd-Sadier, David M. Ojcius, Hsin-Chih Lai

All Dugoni School of Dentistry Faculty Articles

Mycobacterium kansasii has emerged as an important nontuberculous mycobacterium pathogen, whose incidence and prevalence have been increasing in the last decade. M. kansasii can cause pulmonary tuberculosis clinically and radiographically indistinguishable from that caused by Mycobacterium tuberculosis infection. Unlike the widely-studied M. tuberculosis, little is known about the innate immune response against M. kansasii infection. Although inflammasome activation plays an important role in host defense against bacterial infection, its role against atypical mycobacteria remains poorly understood. In this report, the role of inflammasome activity in THP-1 macrophages against M. kansasii infection was studied. Results indicated that viable, but not heat-killed, …

Cloning And Characterization Of The Cell Wall Acting Enzyme Cd1034 From The Pathogen Clostridium Difficile, Zachary Suter

Honors Projects in Science and Technology

The manifestation of multidrug resistance in bacteria over the past several decades has resulted in one of the foremost challenges in the management of infectious diseases. The question arises, “How do we address this growing problem?” One solution to stem the growing rise in antimicrobial resistance is to investigate new targets, while another approach is to re-examine classical antibacterial targets with a fresh perspective. The aim of this paper is to begin the process of antibacterial development for the pathogen Clostridium difficile by characterizing the cell wall acting glucosaminidase CD1034. It is inunderstanding how CD1034 functions biochemically that it can …

Development Of A Humanized Hla-A2.1/Dp4 Transgenic Mouse Model And The Use Of This Model To Map Hla-Dp4-Restricted Epitopes Of Hbv Envelope Protein, Zhitao Ru, Wenjun Xiao, Anthony Pajot, Zhihua Kou, Shihui Sun, Benard Maillere, Guangyu Zhao, David M. Ojcius, Yu-Chun Lone, Yusen Zhou

All Dugoni School of Dentistry Faculty Articles

A new homozygous humanized transgenic mouse strain, HLA-A2.1^+/+HLA-DP4^+/+ hCD4^+/+mCD4^−/−IAβ^−/−β2m^−/− (HLA-A2/DP4), was obtained by crossing the previously characterized HLA-A2^+/+β2m−/− (A2) mouse and our previously created HLA-DP4^+/+ hCD4^+/+mCD4^−/−IAβ^−/− (DP4) mouse. We confirmed that the transgenes (HLA-A2, HLA-DP4, hCD4) inherited from the parental A2 and DP4 mice are functional in the HLA-A2/DP4 mice. After immunizing HLA-A2/DP4 mice with a hepatitis B DNA vaccine, hepatitis B virus-specific antibodies, HLA-A2-restricted and HLA-DP4-restricted responses were observed to be similar to those in naturally infected humans. Therefore, the present …

Glycoinositolphospholipids From Leishmania Braziliensis And L. Infantum: Modulation Of Innate Immune System And Variations In Carbohydrate Structure, Rafael Ramiro Assis, Izabela Coimbra Ibraim, Fátima Soares Noronha, Salvatore J. Turco, Rodrigo Pedro Soares

Molecular and Cellular Biochemistry Faculty Publications

The essential role of the lipophosphoglycan (LPG) of Leishmania in innate immune response has been extensively reported. However, information about the role of the LPG-related glycoinositolphospholipids (GIPLs) is limited, especially with respect to the New World species of Leishmania. GIPLs are low molecular weight molecules covering the parasite surface and are similar to LPG in sharing a common lipid backbone and a glycan motif containing up to 7 sugars. Critical aspects of their structure and functions are still obscure in the interaction with the vertebrate host. In this study, we evaluated the role of those molecules in two medically important …

The Role Of Tumor Suppressors, Ship And Rb, In Immune Suppressive Cells, Michelle Marie Collazo Ruiz

USF Tampa Graduate Theses and Dissertations

Regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC) have been extensively studied in the past 30-40 years. Their potent suppressive capacity shown in several pathological and clinical settings, such as cancer and transplantation, has made it evident that better understanding their development and function is critical.

Specifically, Tregs play a pivotal role in preventing autoimmunity, graft-versus-host disease (GvHD), and organ graft rejection. We previously demonstrated that germline or induced SH2 domain-containing inositol 5-phosphatase (SHIP) deficiency in the host abrogates GvHD. Here we show that SHIP-deficiency promotes an increase of FoxP3+ cells in both the CD4+CD25+ and the CD4+CD25- T …

Toxicological Assessment Of Intra‐Tracheal Instilled Nanoceria On Kidneys Of Sprague‐Dawley Rats, Geeta Nandyala

Theses, Dissertations and Capstones

Recent studies suggest that use of nanoceria in industry is associated with increased risk of human and environmental exposure. How inhaled nanoceria might affect the kidneys is not yet known. To investigate this possibility, Sprague Dawley rats were exposed to a single dose of 7mg/kg body weight cerium oxide nanoparticles by intratracheal instillation. Animals were sacrificed at day 1, 3, 14, or 28 days after exposure and the kidneys collected for histological and biochemical analysis. No significant difference was observed in kidney to body weight ratio between the different groups. Hematoxylin and eosin staining did not reveal any significant changes …

Recent Advances In Biocuration: Meeting Report From The Fifth International Biocuration Conference, Pascale Gaudet, Cecilia Arighi, Frederic Bastian, Alex Bateman, Judith A. Blake, Raja Mazumder, +17 Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

The 5th International Biocuration Conference brought together over 300 scientists to exchange on their work, as well as discuss issues relevant to the International Society for Biocuration’s (ISB) mission. Recurring themes this year included the creation and promotion of gold standards, the need for more ontologies, and more formal interactions with journals. The conference is an essential part of the ISB's goal to support exchanges among members of the biocuration community. Next year's conference will be held in Cambridge, UK, from 7 to 10 April 2013. In the meanwhile, the ISB website provides information about the society's activities (http://biocurator.org …

A Genomic Island In Salmonella Enterica Ssp. Salamae Provides New Insights On The Genealogy Of The Locus Of Enterocyte Effacement., P Scott Chandry, Simon Gladman, Sean C Moore, Torsten Seemann, Keith A Crandall, Narelle Fegan

Computational Biology Institute

The genomic island encoding the locus of enterocyte effacement (LEE) is an important virulence factor of the human pathogenic Escherichia coli. LEE typically encodes a type III secretion system (T3SS) and secreted effectors capable of forming attaching and effacing lesions. Although prominent in the pathogenic E. coli such as serotype O157:H7, LEE has also been detected in Citrobacter rodentium, E. albertii, and although not confirmed, it is likely to also be in Shigella boydii. Previous phylogenetic analysis of LEE indicated the genomic island was evolving through stepwise acquisition of various components. This study describes a new LEE region from two …

Photochemotherapeutic Strategies Against Acanthamoeba Keratitis, Ruqaiyyah Siddiqui, Naveed Ahmed Khan

Department of Biological & Biomedical Sciences

Here, we determined the potential of photochemotherapy, namely the application of photodynamic compounds followed by exposure to a suitable source of UV-visible radiation against corneal pathogen, Acanthamoeba. Organometallic macromolecule, tin porphyrin [Sn(IV)porphyrin] was synthesized and purity confirmed using nuclear magnetic resonance spectroscopy. The Sn(IV)porphyrin was tested against a keratitis isolate of Acanthamoeba castellanii belonging to the T4 genotype using growth and viability assays. The effects of Sn(IV)porphyrin on A. castellanii binding to and cytopathogenicity of human corneal epithelial cells in vitro were tested. The metalloporphyrin showed potent amoebistatic effects. The tin porphyrin inhibited amoebae binding to and cytopathogenicity of corneal …

Exploring Conformational Variability Of An Rna Domain In The Ribosome: From Structure And Function To Potential Antibiotic Targeting, Yogo Sakakibara

Wayne State University Dissertations

RNA in nature is modified at many specific sites to order to gain extra functions or to expand the genetic code. One of such RNAs is ribosomal RNA (rRNA), which contains several modified bases, particularly around the functionally significant sites. We have focused on understanding the influences of modified base on RNA structure and function by employing helix 69 (H69), which is a good region to evaluate the roles of modified bases since it contains three pseudouridines in the loop region and exists at the core of the ribosome.

Previous model studies using small hairpin H69 showed the conformational differences …

In Vivo Display: A Selection And Its Derivatives For Antimicrobial Peptide Lead Identification, Wesley David Colangelo

Wayne State University Dissertations

The rise of antibiotic resistance necessitates new approaches for the isolation of new antimicrobials with novel inhibitory mechanisms, bypassing the development of rapid resistance by modification of pre-existing resistance mechanisms. In response, we have developed a series of systems for the rapid isolation and identification of peptides that inhibit the growth of Escherichia coli and other bacteria, termed in vivo display (IVD).

IVD harnesses the cellular processes of E. coli for the expression of a library of random peptides at the terminus of a display protein. A library of 12-amino acid random peptide sequences was added to either the C- …

An Ims/Atp Assay For The Detection Of Mycobacterium Tuberculosis In Urine, Dawn M. Hunter, Daniel V. Lim

Molecular Biosciences Faculty Publications

Background. Although sputum smears are the gold standard for diagnosis of tuberculosis, sensitivity in HIV/TB coinfection cases is low, indicating a need for alternative methods. Urine is being increasingly evaluated. Materials and Methods. A novel method for detecting Mycobacterium tuberculosis (MTB) in synthetic urine using a combined IMS/ATP assay was evaluated. Preliminary work established standard ATP conditions and the sensitivity and specificity of the MTB antibody. Eighty-four blinded samples in four replicate assays were evaluated for the presence of MTB using labeled immunomagnetic beads for capture. Beads were separated, washed, and resuspended in broth and added to a …

Modulation Of Anti-Tumor Immune Response By Tgf-Β-Inducible Early Gene 1 (Tieg1), Andi Cani

Wayne State University Theses

Cancer immunotherapy has had limited clinical efficacy partly because regulatory T cells (Treg) suppress the immune response to tumor-associated antigens. Inducible regulatory T cells (iTreg), which are converted from naïve CD4 T cells by TGF-β, an abundant cytokine in the tumor microenvironment, may contribute to this immune suppression. Induction of Foxp3 by TGF-β is mediated by the transcription factor TIEG1 and abrogation of this protein prevents Foxp3 expression. We are testing the hypothesis that blockade of TIEG1 to prevent iTreg conversion will enhance immune response in DNA vaccination to the tumor associated antigen Her-2. Wild type and TIEG1 knockout mice …

Use Of Methionine Sulfoximine To Dissect The Role Of Glutamine Synthetase And Glutamine In Progression Of Acute Liver Failure, Amruta Anil Jambekar

Wayne State University Dissertations

Methionine sulfoximine (MSO) is a modified amino acid and a well characterized irreversible inhibitor of glutamine synthetase (GS) enzyme. Glutamine is synthesized by GS enzyme and it is the most abundant amino acid in the body. Glutamine is required by immune cells for generation, propagation and maintenance of an immune response.

To induce acute liver failure (ALF) in mice, animals were given intraperitoneal injections of E. coli lipopolysaccharides (LPS) and sugar D-galactosamine (D-GalN). When these animals were pretreated with MSO, 80% of the animals were completely rescued from liver failure. Moreover, when we characterized the immune response generated during ALF …

Methamphetamine Administration Targets Multiple Immune Subsets And Induces Phenotypic Alterations Suggestive Of Immunosuppression., Robert Z. Harms, Brenda M. Morsey, Craig W. Boyer, Howard S. Fox, Nora E. Sarvetnick

Journal Articles: Regenerative Medicine

Methamphetamine (Meth) is a widely abused stimulant and its users are at increased risk for multiple infectious diseases. To determine the impact of meth on the immune system, we utilized a murine model that simulates the process of meth consumption in a typical addict. Our phenotypic analysis of leukocytes from this dose escalation model revealed that meth affected key immune subsets. Meth administration led to a decrease in abundance of natural killer (NK) cells and the remaining NK cells possessed a phenotype suggesting reduced responsiveness. Dendritic cells (DCs) and Gr-1(high) monocytes/macrophages were also decreased in abundance while Gr-1(low) monocytes/macrophages appear …

Lipase-Kinase Associations Involving Pld2, Jak3 And Fes That Underlie Cancer Cell Proliferation And Invasion, Qing Ye

Browse all Theses and Dissertations

Phospholipase D (PLD) is an enzyme that breaks down phospholipids in the cell membrane. It has been suggested that PLD may play a role during cell proliferation and cell invasion of cancer cells. The objective of this thesis was to define new molecular signaling pathways in which PLD2 might be involved in terms of cell proliferation (first part) and cell invasion (second part). To this, I compared molecular and biochemical aspects between untransformed cell lines with highly invasive, transformed breast cancer cells. In the first part, I investigated the interaction of two tyrosine kinases with PLD2 and the effect of …

Copper–Zinc Superoxide Dismutase-Deficient Mice Show Increased Susceptibility To Experimental Autoimmune Encephalomyelitis Induced With Myelin Oligodendrocyte Glycoprotein 35–55, Chandirasegara Massilamany, Arunakumar Gangaplara, Heejeong Kim, Charlotte Standord, Govardhan Rathnaiah, David Steffen, Jaekwon Lee, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

In this report, we have addressed the role of copper–zinc superoxide dismutase (SOD1) deficiency in the mediation of central nervous system autoimmunity. We demonstrate that SOD1-deficient C57Bl/6 mice develop more severe autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein (MOG) 35–55, compared with wild type mice. This alteration in the disease phenotype was not due to aberrant expansion of MOG-specific T cells nor their ability to produce inflammatory cytokines; rather lymphocytes generated in SOD1-deficient mice were more prone to spontaneous cell death when compared with their wild type littermate controls. The data point to a role for SOD1 in the maintenance …