Biomaterials selectively modulate interactions between human blood-derived polymorphonuclear leukocytes and monocytes.

Implantation of a biomaterial into the body elicits a host foreign body response, during which polymorphonuclear leukocytes (PMNs) and then monocytes (MCs) are recruited to the site of implantation. MCs and MC-derived macrophages are central players in this response because they secrete proinflammatory and/or pro-wound-healing cytokines and growth factors that influence subsequent healing events. Although mechanisms of MC response to biomaterials are often studied in in vitro monoculture models, few studies have investigated how biomaterials modulate PMN-MC paracrine and juxtacrine interactions. To address this, we cultured human blood-derived MCs alone or in the presence of autologous PMN-conditioned medium (PCM) on poly(ethylene glycol) hydrogels, poly(dimethyl siloxane), and tissue culture polystyrene. We also directly co-cultured autologous PMNs and MCs on these biomaterials. PCM increased MC adhesion/viability and expression of IL-1ß and tumor necrosis factor-α in a biomaterial- and time-dependent manner when compared with MCs that were not cultured in PCM. There were also biomaterial- and time-dependent differences in cell adhesion/viability, apoptosis, and expression of IL-6 and IL-8 in the PMN-MC direct co-cultures when compared with the sums of these activities in PMN and MC monocultures. In conclusion, these data suggest that biomaterials selectively modulate PMN-MC paracrine and juxtacrine interactions to influence MC and/or PMN adhesion/viability, apoptosis, and cytokine expression.

Non-cell-autonomous RNA interference in mammalian cells: Implications for in vivo cell-based RNAi delivery.

RNA interference (RNAi) is a post-transcriptional pathway in which double-stranded RNA (dsRNA) triggers the degradation of complementary mRNA in the cytoplasm of eukaryotic cells. In plants and in some animals, including Caenorhabditis elegans, initiation of RNAi in one cell can lead to sequence-specific RNA silencing in another cell, a phenomenon referred to as non-cell-autonomous RNAi. Until recently, this phenomenon had not been observed in mammalian cells. Here, we review emerging data demonstrating that non-cell-autonomous RNAi occurs in cultured mammalian cells. We discuss possible mechanisms for the transfer of RNAi between mammalian cells and highlight the implications of this phenomenon for the development of in vivo cell-based RNAi delivery.

First natural analogs of the cytotoxic thiodepsipeptide thiocoraline A from a marine Verrucosispora sp.

A marine Verrucosispora sp. isolated from the sponge Chondrilla caribensis f. caribensis was found to produce thiocoraline, a potent cytotoxic compound. Five new analogs of thiocoraline were isolated and represent the first analogs of thiocoraline. 22'-Deoxythiocoraline (2), thiochondrilline C (5), and 12'-sulfoxythiocoraline (6) demonstrated significant cytotoxicity against the A549 human cancer cell line with EC(50) values of 0.13, 2.86, and 1.26 µM, respectively. The analogs provide insight into the SAR and biosynthesis of thiocoraline. The DP4 probability method was used to analyze ab initio NMR calculations to confirm stereochemical assignments.