Efferocytosis Signaling in the Regulation of Macrophage Inflammatory Responses.

Since the pioneering work of Elie Metchnikoff and the discovery of cellular immunity, the phagocytic clearance of cellular debris has been considered an integral component of resolving inflammation and restoring function of damaged and infected tissues. We now know that the phagocytic clearance of dying cells (efferocytosis), particularly by macrophages and other immune phagocytes, has profound consequences on innate and adaptive immune responses in inflamed tissues. These immunomodulatory effects result from an array of molecular signaling events between macrophages, dying cells, and other tissue-resident cells. In recent years, many of these molecular pathways have been identified and studied in the context of tissue inflammation, helping us better understand the relationship between efferocytosis and inflammation. We review specific types of efferocytosis-related signals that can impact macrophage immune responses and discuss their relevance to inflammation-related diseases.

Peripheral administration of D-cycloserine rescues memory consolidation following bacterial endotoxin exposure.

In the current study, the partial NMDA receptor agonist D-cycloserine (DCS) rescued memory consolidation following systemic bacterial endotoxin exposure. DCS failed, however, to restore hippocampal BDNF mRNA levels that were diminished following a systemic administration of LPS, and did not alter NR1 or NR2C NMDA receptor subunit expression. These results extend prior research into the role of DCS in neural-immune interactions, and indicate that the detrimental effects of peripheral LPS administration on consolidation of contextual fear memory may be ameliorated with DCS treatment, though the mechanisms underlying these effects are currently unclear.

miRNAs as potential therapeutic targets for age-related macular degeneration.

Since their recent discovery, miRNAs have been shown to play critical roles in a variety of pathophysiological processes. Such processes include pathological angiogenesis, the oxidative stress response, immune response and inflammation, all of which have been shown to have important and interdependent roles in the pathogenesis and progression of age-related macular degeneration (AMD). Here we present a brief review of the pathological processes involved in AMD and review miRNAs and other noncoding RNAs involved in regulating these processes. Specifically, we discuss several candidate miRNAs that show promise as AMD therapeutic targets due to their direct involvement in choroidal neovascularization or retinal pigment epithelium atrophy. We discuss potential miRNA-based therapeutics and delivery methods for AMD and provide future directions for the field of miRNA research with respect to AMD. We believe the future of miRNAs in AMD therapy is promising.

Peripheral administration of poly I:C disrupts contextual fear memory consolidation and BDNF expression in mice.

In the current study, administration of poly I:C induced a deficit in contextual, but not auditory-cue, fear memory consolidation. This memory deficit coincided with a decrease in hippocampal and cortical BDNF mRNA expression. These results extend prior work, and suggest that a single peripheral injection of poly I:C disrupts contextual fear memory consolidation processes in adult mice, and that these deficits may potentially be mediated by diminished BDNF expression.