Activated Protein C Inhibits Pancreatic Islet Inflammation, Stimulates T Regulatory Cells, and Prevents Diabetes in Non-obese Diabetic (NOD) Mice

Xue, Meilang; Dervish, Suat; Harrison, Leonard C.; Fulcher, Gregory; Jackson, Christopher J.

doi:10.1074/jbc.m111.325951

Cited by 34 publications

(29 citation statements)

References 42 publications

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“…LPS administration led to enhanced CD4 + CD25 + Foxp3 + Treg differentiation, but exerted no profound influence on DC phenotype Tregs and DCs participate in the regulation of the immune state of T lymphocytes during the progression of T1D (Sousa, 2006;Hubert et al, 2007;Xue et al, 2012). In the present study, LPS treatmentboth single and multiple injection protocols -increased low levels of CD4 + CD25 + Foxp3 + T cells (Tregs) in NOD mice (Fig.…”

Section: Lps Administration Down-regulated Th1-mediated Autoreactive mentioning

confidence: 48%

“…The development of T1D is mediated by autoreactive T cells, which infiltrate and cause the death of pancreatic β cells. Pathogenic T cells are normally held in check by CD4 + CD25 + Foxp3 + Tregs, which are important components of immune suppression (Xue et al, 2012). Tregs are directly involved in limiting diabetes progression in mice, rats and humans (Caramalho et al, 2011).…”

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 99%

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Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

Wang

Cao

Wang

et al. 2015

Toxicology and Applied Pharmacology

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Section: Lps Administration Down-regulated Th1-mediated Autoreactive mentioning

confidence: 48%

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 99%

Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

Wang

Cao

Wang

et al. 2015

Toxicology and Applied Pharmacology

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“…Macrophages/monocytes can express CD11c under inflammatory conditions without converting into DC (Drutman, Kendall, & Trombetta, 2012; Wentworth et al, 2010). T1D in NOD mice results from inflammatory insulitis (Kaminitz, Yolcu, Mizrahi, Shirwan, & Askenasy, 2013), is exacerbated by intestinal inflammation (Alam et al, 2010) and is blocked by anti-inflammatory therapy (Xue, Dervish, Harrison, Fulcher, & Jackson, 2012), so it was likely that inflammatory myeloid cells are present in these mice. However, we noted that splenic mDC and inflammatory macrophages/monocytes can be distinguished by the differences in the fluorescent intensity of CD11b and CD11c, i.e.…”

Section: Resultsmentioning

confidence: 99%

Transgene expression in various organs post BM-HSC transplantation

et al. 2014

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Gene therapy mediated by bone marrow-derived hematopoietic stem cells (BM-HSC) has been widely used in treating genetic deficiencies in both pre-clinical and clinical settings. Using mitotically inactive cell-targeting lentivirus with separate promoters for our gene of interest (the murine MHC class II (MHCII) chaperone, invariant chain (Ii)) and a GFP reporter, we monitored the expression and function of introduced Ii in various types of professional antigen presenting cells (B cells, macrophages and DC) from different organs (spleen, pancreatic lymph nodes (PLN), BM and blood). Ii and GFP were detected. Ii levels correlated with GFP levels only in macrophages and monocytes from spleen, monocytes from PLN and macrophage precursors from blood. By cell type, Ii levels in PLN cells were more similar to those in spleen cells than to those in blood or BM cells. Functionally, Ii expressed in PLN or spleen had more effect on MHCII abundance than Ii expressed in BM or blood. The results have implications for analysis of the outcomes of gene therapy when both therapeutic and reporter genes are introduced. The findings also have implications for understanding the development of immune molecule function.

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“…This protective effect of therapeutically administered aPC in diabetic pathologies was independently replicated in the NOD-mouse model of autoimmune type-1 diabetes [7]. In this model.…”

Section: Apc-resistance Of Fv Leiden In Diabetesmentioning

confidence: 86%

Inflammation-associated activation of coagulation and immune regulation by the protein C pathway

Weiler

2014

Thrombosis Research

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The inflammation-induced activation of the protein C pathway provides negative feedback inhibition of coagulation and exerts coagulation-independent anti-inflammatory and cytoprotective effects. The balance between these activities of aPC modulates the outcome of diverse inflammatory diseases such as encephalitis, diabetes, and sepsis; and is affected by naturally occurring aPC-resistance of coagulation factor V Leiden.

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Activated Protein C Inhibits Pancreatic Islet Inflammation, Stimulates T Regulatory Cells, and Prevents Diabetes in Non-obese Diabetic (NOD) Mice

Cited by 34 publications

References 42 publications

Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

Transgene expression in various organs post BM-HSC transplantation

Inflammation-associated activation of coagulation and immune regulation by the protein C pathway

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