A5059140393- Immune Response and Inflammation
- Immune Cell Function and Interaction
- interferon and immune responses
- T-cell and B-cell Immunology
- Antimicrobial Peptides and Activities
- NF-κB Signaling Pathways
- Immunotherapy and Immune Responses
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Adipokines, Inflammation, and Metabolic Diseases
- Cytokine Signaling Pathways and Interactions
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Monoclonal and Polyclonal Antibodies Research
- Influenza Virus Research Studies
- Neonatal Respiratory Health Research
- Vitamin C and Antioxidants Research
- Inflammasome and immune disorders
- Cytomegalovirus and herpesvirus research
- RNA Interference and Gene Delivery
- Immunodeficiency and Autoimmune Disorders
- Adipose Tissue and Metabolism
- Retinal Development and Disorders
- RNA modifications and cancer
- Endoplasmic Reticulum Stress and Disease
The University of Texas Southwestern Medical Center
2016-2025
Southwestern Medical Center
2012-2023
Scripps Research Institute
2006-2015
Wayne State University
2010
La Jolla Bioengineering Institute
2010
University of California, San Diego
2004-2010
Rockefeller University
1985-2008
Université Paris Cité
2006
Inserm
2006
Shanghai Institute of Hematology
2006
Mutations of the gene Lps selectively impede lipopolysaccharide (LPS) signal transduction in C3H/HeJ and C57BL/10ScCr mice, rendering them resistant to endotoxin yet highly susceptible Gram-negative infection. The codominant d allele mice was shown correspond a missense mutation third exon Toll-like receptor-4 ( Tlr4 ), predicted replace proline with histidine at position 712 polypeptide chain. are homozygous for null . Thus, mammalian protein has been adapted primarily subserve recognition...
Cachectin (tumor necrosis factor), a protein produced in large quantities by endotoxin-activated macrophages, has been implicated as an important mediator of the lethal effect endotoxin. Recombinant human cachectin was infused into rats effort to determine whether cachectin, itself, can elicit derangements host physiology caused administration When administered similar those endogenously response endotoxin, causes hypotension, metabolic acidosis, hemoconcentration, and death within minutes...
A highly specific polyclonal rabbit antiserum directed against murine cachectin/tumor necrosis factor (TNF) was prepared. When BALB/c mice were passively immunized with the or purified immune globulin, they protected lethal effect of endotoxin lipopolysaccharide produced by Escherichia coli . The prophylactic dose-dependent and most effective when administered prior to injection endotoxin. Antiserum cachectin/TNF did not mitigate febrile response endotoxin-treated animals, very high doses...
Recently, cDNA sequences have been reported for both human and murine tumor necrosis factor (TNF; cachectin). The coding region of the TNF genes is highly conserved between man mouse; 80% homology apparent at amino acid level. We now observe that a 33-nucleotide sequence, comprised entirely A T residues located in 3'-untranslated region, toto mRNAs. Since normally not conserved, we reasoned this sequence might play regulatory role. identified consensus (TTATTTAT) present mouse mRNAs, as well...
Recombinant human tumor necrosis factor (rTNF alpha) injected intravenously into rabbits produces a rapid-onset, monophasic fever indistinguishable from the produced by rIL-1. On weight basis (1 microgram/kg) rTNF alpha and rIL-1 produce same amount of induce comparable levels PGE2 in rabbit hypothalamic cells vitro; like IL-1, TNF is blocked drugs that inhibit cyclooxygenase. At higher doses (10 micrograms/kg) biphasic fevers. The first reaches peak elevation 45-55 min after bolus injection...
Cachectin (tumor necrosis factor) is a macrophage hormone strongly implicated in the pathogenesis of endotoxin-induced shock. The availability DNA probe complementary to cachectin messenger RNA (mRNA), as well specific antibody capable recognizing gene product, has made it possible analyze regulation expression under variety conditions. Thioglycollate-elicited peritoneal macrophages obtained from mice contain pool mRNA that not expressed protein. When cells are stimulated with endotoxin,...
Cachectin/TNF (tumor necrosis factor), an endotoxin-induced murine macrophage hormone implicated in the pathogenesis of cachexia and shock, has been found capable stimulating collagenase prostaglandin E2 (PGE2) production by isolated human synovial cells dermal fibroblasts. This bioactivity associated with cachectin is comparable to that observed monokine interleukin 1 (IL-1), previously suggested as major mediator proteolysis. The ability cachectin/TNF stimulate PGE2 suggests it may play a...
The innate immune system recognizes viral dsRNA through two distinct pathways; the Toll-like receptor 3 (TLR3) pathway detects phagocytosed in endosomes; helicases retinoic acid-induced protein I (RIG-I) and melanoma differentiation-associated gene-5 (mda-5) detect cytoplasmic generated during replication. Both RIG-I mda-5 can bind polyriboinosinic:polyribocytidylic acid (polyI:C), synthetic analog of dsRNA, mediate type IFN responses to polyI:C multiple RNA viruses vitro. We mda-5-deficient...
Several subsets of dendritic cells have been shown to produce type I IFN in response viral infections, thereby assisting the natural killer cell-dependent that eliminates pathogen. Type production can be induced both by unmethylated CpG-oligodeoxynucleotide and double-stranded RNA. Here, we describe a codominant CpG-ODN unresponsive phenotype results from an N -ethyl- -nitrosourea-induced missense mutation Tlr9 gene ( CpG1 ). Mice homozygous for allele are highly susceptible mouse...
Previous studies have indicated that endotoxin and other bacterial protozoal products can stimulate macrophages to produce a factor suppress the activity of enzyme lipoprotein lipase (LPL), in vivo vitro. In present report we describe purification this factor, cachectin, apparent homogeneity from conditioned medium endotoxin-stimulated RAW 264.7 cells. The isolated protein has an isoelectric point 4.7 subunit molecular weight 17,000. Although cachectin's are similar those described for...