Caspase-1 activation is a central event in innate immune responses to many pathogenic infections and tissue damage. The NLRP3 inflammasome, a multi-protein scaffolding complex that assembles in response to two distinct steps, priming and activation, is required for caspase-1 activation. However the detailed mechanisms of these steps remain poorly characterized. To investigate the process of LPS mediated NLRP3 inflammasome priming we used constitutively present proIL-18 as the caspase-1 specific substrate to allow study of the early events. We analyzed human monocyte caspase-1 activity in response to LPS priming followed by activation with ATP. Within minutes of endotoxin priming, the NLRP3 inflammasome is licensed for ATP induced release of processed IL-18, ASC, and active caspase-1, independent of new mRNA or protein synthesis. Moreover, extracellular-regulated kinase 1 (ERK1) phosphorylation is central to the priming process. ERK inhibition and siRNA mediated ERK1 knockdown profoundly impair priming. In addition, proteasome inhibition prevents ERK phosphorylation and blocks priming. Scavenging reactive oxygen species (ROS) with diphenylene-iodonium also blocks both priming and ERK phosphorylation. These findings suggest that ERK1-mediated post-translational modifications license the NLRP3 inflammasome to respond to the second signal ATP by inducing posttranslational events that are independent of new production of proIL-1β and NOD-like receptor components.

Oncolytic viral therapy has gained significant traction as cancer therapy over the past 2 decades. Oncolytic viruses are uniquely designed both to lyse tumor cells through their replication and to recruit immune responses against virally infected cells. Increasingly, investigators are leveraging this immune response to target the immunosuppressive tumor microenvironment and improve immune effector response against bystander tumor cells. In this article, we review the spectrum of preclinical, early-stage clinical, and potential future efforts with cytokine-secreting oncolytic viruses, with a focus on the treatment of brain tumors and solid tumors.

A group of medicinal plant including Silene (Silene nocturna), Black seed (Nigella sativa) and Chamomile (Matricaria chamomilla) growing in Egypt were examined for their immunomodulatory effect in Balb/c mice. Treatment (intraperitoneal injection) with five doses of methanolic extract for each plant was found to enhance the total white blood cells count (up to 1.2 × 10(4) cells/mm(3)). Bone marrow cellularity also increased significantly (P < 0.01) after the administration of the extract of each of three test plants. Furthermore, spleen weight of the treated groups was significantly increased (P < 0.01). Two groups of mice were immunosuppressed with cyclophosphamide, the one which pretreated with the plants extracts significantly (P < 0.01) restored their resistance against lethal infection with the predominately granulocyte-dependant Candida albicans. These results confirm the immunomodulatory activity of Silene, Black seed, and Chamomile extracts and may have therapeutical implications in prophylactic treatment of opportunistic infections and as supportive treatment in oncogenic cases.