Abstract Active episodes of the inflammatory bowel diseases are associated with infiltration large numbers myeloid cells including neutrophils, monocytes, and macrophages. The objective this study was to systematically characterize define different populations generated in a mouse model chronic gut inflammation. Using T cell transfer colitis, we found that induction disease enhanced production myelopoietic cytokines (IL-17 G-CSF), increased neutrophils into mesenteric lymph nodes (MLNs)...

The major risk factors for intracerebral hemorrhage (ICH) are hypertension and aging. A fundamental mechanism hypertension- aging-induced vascular injury is oxidative stress. We hypothesize that stress has a crucial role in ICH. To test our hypothesis, we used bacterial collagenase to produce ICH wild-type C57BL/6 gp91phox knockout (gp91phox KO) mice (deficient subunit of the superoxide-producing enzyme NADPH oxidase). All animals were studied at 20-35 weeks age, resembling an older patient...

One of the best characterized mouse models inflammatory bowel diseases (IBD; Crohn's disease, ulcerative colitis) is CD4+CD45RBhigh T cell transfer model chronic colitis. Following our relocation to Texas Tech University Health Sciences Center (TTUHSC), we observed a dramatic reduction in incidence moderate-to-severe colitis from 16-year historical average 90% at Louisiana State (LSUHSC) <30% TTUHSC. We hypothesized that differences commensal microbiota 2 institutions may account for...

Recent clinical trials indicate the efficacy of interferon (IFN)-β1b in reducing relapse rate relapsing-remitting multiple sclerosis (MS), whereas a surge IFN-γ precedes and provokes acute relapses. Disruption cerebral endothelial barrier transendothelial migration inflammatory cell into brain play significant role pathogenesis MS may be driven by this IFN-γ. However, molecular mechanisms underlying beneficial effects IFN-β1b against deleterious on formed junctional proteins remain to...

It is well known that transfer of CD4+CD45RBhigh (naïve) T cells into syngeneic lymphocyte-deficient mice induces chronic colitis. However, no studies have reported the presence small bowel inflammation in this cell-dependent model. Therefore, objective study was to evaluate and compare large induced by naïve two different immunodeficient recipient mice. B cell-deficient recombinase activating gene 1-deficient [RAG knockout (KO)] cell receptor-beta x receptor-delta double-deficient (TCR KO)...

Disruption of the blood brain barrier (BBB) and transendothelial migration inflammatory cells are crucial steps in development demyelinating lesions multiple sclerosis (MS). Occludin vascular endothelial-cadherin (VE-cadherin) two major components tight junctions (TJs) microvasculature that help to create BBB. In present study, we investigated effect serum from MS patients on expression these junctional markers endothelial integrity. Serum six exacerbation, remission, normal controls (10% by...

Inflammation-associated lymphangiogenesis (IAL) is frequently observed in inflammatory bowel diseases. IAL believed to limit inflammation by enhancing fluid and immune cell clearance. Although monocytes/macrophages (MΦ) are known contribute intestinal pathology disease, their role has never been studied mechanistically. We investigated contributions of monocytes/MΦ the development IAL.Because monocytes express CC chemokine receptor 2 (CCR2), we used CCR2 diphtheria toxin transgenic...

The β2 integrin lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) is important for trafficking and activation as well recruitment to sites of tissue inflammation. objective this study was assess the role 'T-cell-associated' LFA-1 in pathogenesis chronic colitis vivo. Transfer CD4+CD25− T cells isolated from wild-type (wt) mice into immunodeficient recipients [recombinase-activating gene-1-deficient (RAG-1−/−)] produced moderate severe colitis, whereas RAG-1−/− injected with...

Clinical trials and animal studies have revealed a role for the renin-angiotensin system in enhanced thrombus development that is associated with hypertension. Because T lymphocytes been implicated vascular dysfunction blood pressure elevation increased angiotensin II (Ang II) levels, we evaluated of adaptive immune mediating thrombosis during Ang II-induced Light/dye-induced was induced cremaster arterioles wild-type, immunodeficient Rag-1(-/-), CD8(+), or CD4(+) lymphocyte-deficient NADPH...

Background and Purpose The lymphatic system maintains tissue homeostasis by unidirectional lymph flow, maintained tonic phasic contractions within subunits, ‘lymphangions’. Here we have studied the effects of inflammatory cytokine IL ‐1β on contraction rat mesenteric muscle cells ( RMLMC ). Experimental Approach We measured in colon‐conditioned media CM ) from acute AC‐CM , dextran sodium sulfate) chronic CC‐CM T‐cell transfer) colitis‐induced mice corresponding controls C on‐ AC / examined...

It is strongly suspected that cytokine-induced gene expression in inflammation oxidant mediated; however, the intracellular sources of signaling oxidants remain controversial. In inflammatory bowel disease (IBD) proinflammatory cytokines, such as TNF-α, trigger endothelial adhesion molecules including mucosal addressin cell molecule-1 (MAdCAM-1). MAdCAM-1 plays an essential role gut by governing infiltration leukocytes into intestine. Several groups suggest endothelial-derived reduced NADP...

Donor-specific blood transfusion (DST) prior to solid organ transplantation has been shown induce long-term allograft survival in the absence of immunosuppressive therapy. Although mechanisms underlying DST-induced tolerance are not well defined, there is evidence suggest DST induces one or more populations antigen-specific regulatory cells that suppress rejection. However, neither identity nor properties these tolerogenic lymphocytes have reported. Therefore, objective this study was define...

Abstract Chronic colitis is accompanied by extensive myelopoiesis and accumulation of CD11b+Gr-1+ cells in spleens secondary lymphoid tissues. Although with similar phenotype have been described cancer, chronic infection, or autoimmunity, where they were associated suppression T cell responses, little known regarding how these affect CD4 responses the context intestinal inflammation. Therefore, we undertook this study to characterize interplay between colitis-induced myeloid cell. Within...

The induction and perpetuation of chronic colitis are thought to involve a complex set adhesive interactions between T cells endothelial located on the vasculature within secondary lymphoid tissue intestine. objective this study was assess roles cell-associated CD18, CD62L (L-selectin), ICAM-1, P-selectin glycoprotein ligand-1 (PSGL-1) in mice. CD4(+)CD25(-) derived from either wild-type (WT), CD18-deficient [CD18 knockout (KO)], KO, ICAM-1 or PSGL-1 KO mice were adoptively transferred into...

Inflammatory arthritis is a chronic disease, resulting in synovitis and subchondral bone area destruction, which can severely affect patient's quality of life. The most common form inflammatory rheumatoid (RA) many the disease mechanisms are not well understood. collagen-induced (CIA) mouse model similar to RA as it exhibits joint space narrowing erosion involves factors cellular players that have been implicated pathogenesis. Quantitative data for progression models difficult obtain serum...

BackgroundIt is well known that enteric bacterial antigens drive the development of chronic colitis in a variety different mouse models inflammatory bowel diseases (IBD). The objective this study was to evaluate role gut-associated lymphoid tissue (GALT; Peyer's patches, isolated follicles), mesenteric lymph nodes (MLNs) and spleen pathogenesis mice.

We demonstrate a novel strategy using affinity extraction (AE) LC-MS to directly measure drug exposure and target engagement, two critical pharmacological questions, with single assay. The assay measures total concentration at the site of therapeutic action, as well amount bound drug. case study presented applies engagement membrane receptor (CD40) that is immune regulation in colon biopsies collected from monkey dosed an anti-CD40 antibody. Unlike other techniques occupancy, such flow...

Mesenchymal stem cells (MSC) have immune regulatory properties that may ameliorate pathophysiological processes in sepsis. We determined the effect of allogeneic adipose-derived MSCs (Cx611) on host response during sepsis due to community-acquired bacterial pneumonia (CABP) by measuring 29 plasma biomarkers and blood transcriptomes at six time points 82 patients randomised two intravenous infusions Cx611 or placebo. treatment enhanced several endothelial cell procoagulant biomarkers, led...

Cytomegalovirus has been implicated in cardiovascular disease, possibly through the induction of inflammatory processes. P-selectin and L-selectin are adhesion molecules that mediate early microvascular responses to stimuli. This study examined role these selectins dysfunction occurs during persistent CMV infection. C57Bl/6, P- or L-selectin-deficient mice were mock-inoculated infected with murine CMV, five weeks later placed on normal diet high cholesterol for six weeks. expression was...

L-selectin (CD62L) and β7 integrins are important for trafficking of naive T cells under steady-state conditions. The objectives this study were to dissect the requirements cell–associated CD62L during initiation, progression, regulation chronic colitis. Using T-cell transfer model, we compared colitogenic potential between lacking one or both these molecules with wild-type cells. To assess secondary lymphoid tissue gut, performed co-homing experiments. Adoptive wild-type, CD62L−/− β7−/−...