AIM Pancreatic regenerating protein (reg I) stimulates pancreatic regeneration after pancreatectomy and is mitogenic to ductal and beta-cells. This suggests that reg I and its receptor may play a role in recovery after pancreatic injury. We hypothesized that reg I and its receptor are induced in acute pancreatitis. METHODS Acute pancreatitis was induced in male Wistar rats by retrograde injec...

Increasing evidence supports the existence of elevated numbers of regulatory T cells (T(reg) cells) in solid tumors and hematologic malignancies. Whereas the biology of CD4(+)CD25(+)FOXP3(+) T(reg) cells in murine models seems to be rather straightforward, studies in human diseases are more difficult to interpret due to expression of CD25 on activated effector T cells as well as T(reg) cells. M...

The present study aimed at exploring the potential of the P-glycoprotein (P-gp) transporters as a barrier to the repaglinide (REG) epithelial permeability. In-vitro intestinal absorption models, the everted gut sac, and Caco-2 cell line, were used to study the possible role of P-gp in intestinal transport of REG. In the everted gut sacs, apparent permeability coefficients showed cargo concentra...

The immunosuppressive drugs rapamycin and cyclosporin A (CsA) are widely used to prevent allograft rejection. Moreover, they were shown to be instrumental in experimental models of tolerance induction. However, it remains to be elucidated whether these drugs have an effect on the CD4+ CD25+ regulatory T-cell (T(REG)) population, which plays an important role in allograft tolerance. Recently, we...

Regulatory T cells (T(reg) cells) maintain immune homeostasis by limiting inflammatory responses. SOCS1 (suppressor of cytokine signaling 1), a negative regulator of cytokine signaling, is necessary for the suppressor functions of T(reg) cells in vivo, yet detailed mechanisms remain to be clarified. We found that Socs1(-/-) T(reg) cells produced high levels of IFN-γ and rapidly lost Foxp3 when ...

Regulatory T cells (T reg cells) constitute a population of CD4(+) T cells that limits immune responses. The transcription factor Foxp3 is important for determining the development and function of T reg cells; however, the molecular mechanisms that trigger and maintain its expression remain incompletely understood. In this study, we show that mice deficient for the Ets-1 transcription factor (E...

As one of the main mediators of the endoplasmic reticulum unfolded protein response, heat shock protein gp96 is also an obligate chaperone for multiple TLRs including TLR4. We demonstrated recently that enforced cell surface expression of gp96 in a transgenic (Tg) mouse (96tm-Tg) conferred hyperresponsiveness to LPS and induced TLR4-dependent lupus-like autoimmune diseases. In this study, we in...

CD4(+)CD25(+)FoxP3(+) regulatory T cells (T reg cells) play a major role in the control of immune responses but the factors controlling their homeostasis and function remain poorly characterized. Nicotinamide adenine dinucleotide (NAD(+)) released during cell damage or inflammation results in ART2.2-mediated ADP-ribosylation of the cytolytic P2X7 receptor on T cells. We show that T reg cells ex...

During thymopoiesis, a unique program of gene expression promotes the development of CD4 regulatory T (T reg) cells. Although Foxp3 maintains a pattern of gene expression necessary for T reg cell function, other transcription factors are emerging as important determinants of T reg cell development. We show that the NF-kappaB transcription factor c-Rel is highly expressed in thymic T reg cells a...