A5009031195- Monoclonal and Polyclonal Antibodies Research
- Biosimilars and Bioanalytical Methods
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Inflammatory Bowel Disease
- IL-33, ST2, and ILC Pathways
- Immunotoxicology and immune responses
- Cytokine Signaling Pathways and Interactions
- Helicobacter pylori-related gastroenterology studies
- Immunotherapy and Immune Responses
- Animal testing and alternatives
- Photodynamic Therapy Research Studies
- Protein purification and stability
- CAR-T cell therapy research
- Pharmaceutical studies and practices
- Chemokine receptors and signaling
- Radiopharmaceutical Chemistry and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Cell Adhesion Molecules Research
- Microscopic Colitis
- NF-κB Signaling Pathways
- Asthma and respiratory diseases
- Computational Drug Discovery Methods
- Animal Genetics and Reproduction
- Reproductive System and Pregnancy
Trident Systems (United States)
2024-2025
Pfizer (United States)
2013-2024
Merck & Co., Inc., Rahway, NJ, USA (United States)
2010
University of California, San Francisco
1997
Medical College of Wisconsin
1997
Cellular Research (United States)
1996
Lafayette School Corporation
1996
Genetic Information Research Institute
1996
Veterinary Medical Teaching Hospital
1988-1993
University of California, Davis
1988-1993
A T helper cell type 1–mediated colitis develops in severe combined immunodeficient mice after transfer of CD45RBhigh CD4+ cells and can be prevented by cotransfer the CD45RBlow subset. The immune-suppressive activities population reversed vivo administration an anti-transforming growth factor β antibody. Here we show that interleukin (IL)-10 is essential mediator regulatory functions population. This isolated from IL-10–deficient (IL-10−/−) was unable to protect when transferred alone...
We have characterized the progressive stages of chronic intestinal inflammation that develops spontaneously in specific pathogen-free (SPF) mice with a targeted disruption IL-10 gene (IL-10-/-). Our longitudinal studies showed inflammatory changes first appear cecum, ascending and transverse colon 3-wk-old mutants. As disease progressed, lesions appeared remainder rectum. Some aged IL-10-/- also developed small intestine. Prolonged transmural high incidence colorectal adenocarcinomas (60%)...
CD4+ T cells in the mouse can be subdivided into two fractions based on level of expression CD45RB determinant. Previous studies have shown that these subsets are functionally distinct. We further characterized properties subpopulations vivo by injecting them C. B-17 scid mice. The animals restored with CD45RBhighCD4+ cell population developed a lethal wasting disease severe mononuclear infiltrates colon and elevated levels IFN-γ mRNA. In contrast, reciprocal CD45RBlow subset or...
A T helper type 1 (Th1)-mediated colitis with similarities to inflammatory bowel disease in humans developed severe combined immunodeficiency mice reconstituted CD45RB(high) CD4+ splenic cells and could be prevented by cotransfer of CD45RB(low) cells. Inhibition this Th1 response the cell population reversed vivo an anti-transforming growth factor (TGF) beta antibody. Interleukin (IL) 4 was not required for either differentiation function protective as from IL-4-deficient were fully...
Human herpesvirus 8 (HHV8, also known as Kaposi's sarcoma [KS]-associated herpesvirus) has been implicated an etiologic agent for KS, angiogenic tumor composed of endothelial, inflammatory, and spindle cells. Here, we report that transgenic mice expressing the HHV8-encoded chemokine receptor (viral G protein-coupled receptor) within hematopoietic cells develop angioproliferative lesions in multiple organs morphologically resemble KS lesions. These are characterized by a spectrum changes...
Mice rendered deficient in the production of interleukin 10 (IL-10-/-) develop a chronic inflammatory bowel disease (IBD) that predominates colon and shares histopathological features with human IBD. Our aim was to identify which cell type(s) can mediate colitis IL-10-/- mice. We detected an influx immunoglobulin-positive cells into presence colon-reactive antibodies serum To assess pathogenic role for B cells, we generated cell-deficient (B-/-) strain B-/-IL-10-/- mice acquired severe...
We have used interleukin-10 (IL-10) gene knockout mice (IL-10−/−) to examine the role of endogenous IL-10 in allergic lung responses Aspergillus fumigatus Ag. In vitro restimulated cells from sensitized IL-10−/− produced exaggerated amounts IL-4, IL-5, and interferon-γ (IFN-γ) compared with wild-type (WT) cells. vivo, significance regulating repeated A. inhalation was strikingly revealed outbred that had a 50–60% mortality rate, while rare similarly treated WT mice. Furthermore, exhibited...
p19, a molecule structurally related to IL-6, G-CSF, and the p35 subunit of IL-12, is recently discovered cytokine IL-23. Here we show that expression p19 in multiple tissues transgenic mice induced striking phenotype characterized by runting, systemic inflammation, infertility, death before 3 mo age. Founder animals had infiltrates lymphocytes macrophages skin, lung, liver, pancreas, digestive tract were anemic. The serum concentrations proinflammatory cytokines TNF-alpha IL-1 elevated,...
We have examined the role of endogenously produced interleukin (IL) 4 and IL-10 in regulation inflammatory immune reactions skin. In these experiments, irritant contact hypersensitivity (CH) responses were elicited mice with targeted disruptions IL-4 (IL-4T) or (IL-10T) gene. Our study showed that IL-4T wild-type (wt) exhibited equivalent to croton oil. contrast, response IL-10T challenged oil was abnormally increased. When exposed a higher dose irritant, irreversible tissue damage occurred....
Abstract IL-10-deficient (IL-10−/−) mice develop chronic enterocolitis mediated by CD4+ Th1 cells producing IFN-γ. Because IL-12 can promote development and IFN-γ production, the ability of neutralizing anti-IL-12 mAb to modulate colitis in IL-10−/− was investigated. Anti-IL-12 treatment completely prevented disease young mice. Treatment adult resulted significant amelioration established accompanied reduced numbers mesenteric lymph node colonic T spontaneously In contrast, anti-IFN-γ had...
Abstract Experimental autoimmune encephalomyelitis (EAE), a T cell-mediated inflammatory disease of the CNS, is rodent model human multiple sclerosis. IL-23 one critical cytokines in EAE development and currently believed to be involved maintenance encephalitogenic responses during tissue damage effector phase disease. In this study, we show that cells from myelin oligodendrocyte glycopeptide (MOG)-immunized wild-type (WT) mice caused indistinguishable when adoptively transferred WT or...
The presenilin containing γ-secretase complex is responsible for the regulated intramembraneous proteolysis of amyloid precursor protein (APP), Notch receptor, and a multitude other substrates. γ-Secretase catalyzes final step in generation Aβ<sub>40</sub> Aβ<sub>42</sub> peptides from APP. Amyloid β-peptides (Aβ peptides) aggregate to form neurotoxic oligomers, senile plaques, congophilic angiopathy, some cardinal pathologies associated with Alzheimer9s disease. Although inhibition this...
Previous studies have shown that the chronic inflammation observed in colon of IL-10-deficient (IL-10(-/-)) mice is mediated by CD4+ Th1 T cells and dependent on presence IFN-gamma for its initial development. As from IL-10(-/-) will cause colitis when transferred into recombinase-activating gene (Rag)-deficient recipients, we considered possibility recipients' NK could be an important source development colitis. Therefore, ability to Rag-deficient recipients had been depleted was tested....
Experimental autoimmune encephalomyelitis (EAE), a Th1-mediated inflammatory disease of the central nervous system (CNS), is model human multiple sclerosis. Cytosolic phospholipase A2α (cPLA2α), which initiates production prostaglandins, leukotrienes, and platelet-activating factor, present in EAE lesions. Using myelin oligodendrocyte glycoprotein (MOG) immunization, as well an adoptive transfer model, we showed that cPLA2α−/− mice are resistant to EAE. Histologic examination CNS from...
This continuing education course was designed to provide an overview of the immunologic mechanisms involved in immunogenicity and hypersensitivity reactions following administration biologics nonclinical toxicity studies, methods used determine whether such are occurring, associated clinical anatomic pathology findings. Hypersensitivity have classically been divided into type I, II, III, IV reactions; I III those most often observed biologics. A variety can be detect these reactions....
Tissue cross-reactivity (TCR) studies are screening assays recommended for antibody and antibody-like molecules that contain a complementarity-determining region (CDR), primarily to identify off-target binding and, secondarily, sites of on-target were not previously identified. At the present time, TCR involve ex vivo immunohistochemical (IHC) staining panel frozen tissues from humans animals, conducted prior dosing humans, results filed with initial IND/CTA support first-in-human clinical...
We used quantitative PCR to investigate the expression of chemokines and chemokine receptors in two Th1-mediated murine models inflammatory bowel disease (IBD). First, mRNA levels encoding MIG, RANTES, lymphotactin, MIP-3α, TCA-3, TARC, MIP-3β, LIX, MCP-1 MIP-1β CCR4, CCR6 CCR2 were significantly increased chronically inflamed colons IL-10– / – mice when compared with wild-type mice. Interestingly, reversal colitis by anti-IL-12 mAb was accompanied inhibition MCP-1, whereas MIP-1β, TARC...