Players In Host Response Research Articles

Assessment of a long-term in vitro model to characterize the mechanical behavior and macrophage-mediated degradation of a novel, degradable, electrospun poly-urethane vascular graft

An assessment tool to evaluate the degradation of biodegradable materials in a more physiological environment is still needed. Macrophages are critical players in host response, remodeling and degradation. In this study, a cell culture model using monocyte-derived primary macrophages was established to study the degradation, macro-/micro-mechanical behavior and inflammatory behavior of a new designed, biodegradable thermoplastic polyurethane (TPU) scaffold, over an extended period of time in vitro. For in vivo study, the scaffolds were implanted subcutaneously in a rat model for up to 36 weeks. TPU scaffolds were fabricated via the electrospinning method. This technique provided a fibrous scaffold with an average fiber diameter of 1.39 ± 0.76 μm and an average pore size of 7.5 ± 1.1 μm. The results showed that TPU scaffolds supported the attachment and migration of macrophages throughout the three-dimensional matrix. Scaffold degradation could be detected in localized areas, emphasizing the role of adherent macrophages in scaffold degradation. Weight loss, molecular weight and biomechanical strength reduction were evident in the presence of the primary macrophage cells. TPU favored the switch from initial pro-inflammatory response of macrophages to an anti-inflammatory response over time both in vitro and in vivo. Expression of MMP-2 and MMP-9 (the key enzymes in tissue remodeling based on ECM modifications) was also evident in vitro and in vivo. This study showed that the primary monocyte-derived cell culture model represents a promising tool to characterize the degradation, mechanical behavior as well as biocompatibility of the scaffolds during an extended period of observation.

Sphingolipids role in the regulation of inflammatory response: From leukocyte biology to bacterial infection.

Sphingolipids (SLs) are amphiphilic molecules mainly associated with the external leaflet of eukaryotic plasma membrane, and are structural membrane components with key signaling properties. Since the beginning of the last century, a large number of papers described the involvement of these molecules in several aspects of cell physiology and pathology. Several lines of evidence support the critical role of SLs in inflammatory diseases, by acting as anti- or pro-inflammatory mediators. They are involved in control of leukocyte activation and migration, and are recognized as essential players in host response to pathogenic infection. We propose here a critical overview of current knowledge on involvement of different classes of SLs in inflammation, focusing on the role of simple and complex SLs in pathogen-mediated inflammatory response.

Establishment of the role of IL-6 and TNF receptor 1 using gene knockout mice

Cytokines are known to be key players in host response to infection, immunological disorders, and tissue injury in the attempt of an organism to overcome the insult and restore homeostasis. Another important aspect of cytokines, however, is their normal physiological role during development in the unchallenged organism. The most elegant way to analyze both of these functions is to introduce targeted mutations in embryonic stem cells in order to create new mouse strains deficient for a given cytokine and identify the functions that are consequently impaired or lost. This review summarizes the mutant phenotypes of mice carrying a null mutation in the cytokine IL-6 gene or the tumor necrosis factor receptor 1 (Tnfr1) gene. Results for interferon-- and interferon-gamma receptor-deficient mice are included for comparison.