MDSCs have been recently implicated in costimulation blockade-induced transplantation tolerance in rats, which was under the control of inducible NO synthase (iNOS). Herein, we describe CD11b+GR-1+MDSC-compatible cells appearing after repetitive injections of lipopolysaccharide (LPS) using a unique mechanism of suppression. These cells suppressed T-cell proliferation and Th1 and Th2 cytokine production

in both mixed lymphocyte reaction and polyclonal stimulation assays. Transfer of CD11b+ cells from LPS-treated mice in untreated recipients significantly prolonged skin allograft survival. They produced large amounts of IL-10 and expressed heme oxygenase-1 (HO-1), a stress-responsive enzyme endowed with immunoregulatory and cytoprotective properties not previously associated with MDSC activity. JNK-IN-8 HO-1 inhibition by the specific inhibitor, SnPP, completely abolished T-cell suppression and IL-10 production. In contrast, neither iNOS nor arginase 1 inhibition did affect suppression. Importantly, selleck kinase inhibitor HO-1 inhibition before CD11b+ cell transfer prevented the delay of allograft

rejection revealing a new MDSC-associated suppressor mechanism relevant for transplantation.”
“Background : Surgical resection is the treatment of choice of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. However, the benefit of clearing resection margin is still controversial. Methods : We reviewed 281 surgically resected cases of IPMN. The recurrences were compared according to the histologic grade (benign BLZ945 solubility dmso or borderline IPMN, malignant noninvasive IPMN, invasive carcinoma)

and size (pancreatic intraepithelial neoplasia, PanIN, less than 0.5 cm in the long axis; and IPMN, greater than or equal to 0.5 cm) of the residual lesions at the resection margin. Results : Sixty cases (21.4%) were invasive carcinoma, and 221 (78.6%) noninvasive cases included 87(31.0%) benign, 107(38.1%) borderline and 11(3.9%) malignant noninvasive IPMN cases. In noninvasive IPMN, increased recurrence in patients with five or more years of follow-up was only related to the involvement of resection margin by severe dysplasia. The recurrence of invasive carcinoma was high (27.3%) even when the resection margin was clear, and was not related to the grade or size of residual tumors at the resection margin. Conclusions : Invasiveness is a strong risk factor for recurrence in IPMN regardless of the status of the resection margin.