coli lipopolysaccharide ( Araújo et al., 2010). Despite the low number of BMDMCs, ultrastructural analysis showed the repair of damaged lungs, suggesting a possible role of paracrine release of trophic factors by, or induced by, BMDMC. In this line, Aslam et al. (2009) demonstrated that the administration MSC-conditioned media was able to reproduce the effects of cell delivery

in a hyperoxia induced pulmonary ALI model. It has been reported that IL-6 and IL-1β can regulate neutrophil trafficking during the inflammatory response by orchestrating chemokine production and leukocyte apoptosis (Fielding et al., 2008). In the current study, BMDMC therapy yielded a reduction in the level of IL-6 and IL-1β at day 1, with a further decrease in IL-6 at day 7 in CLP group, which Nutlin-3a molecular weight may result in a decrease in neutrophil infiltration (Fig. 8). Conversely, IL-10 levels increased after BMDMC administration at

days 1 and 7, with no significant differences between early and late time of analysis. IL-10 has been reported to inhibit the rolling, adhesion, and transepithelial migration of neutrophils contributing to reduce the inflammatory process (Perretti et al., 1995). Similarly, Nemeth et al. (2009) have proposed that the beneficial effects of MSC in experimental CLP induced sepsis were due to the increase in IL-10 production. In contrast, Mei et al. (2010) observed that systemic IL-10 levels Obeticholic Acid research buy were not increased by MSC treatment. These differences may be attributed to the moment of cell administration resulting in a different cytokine profile. In this line, MSCs were delivered 24 h before (Nemeth et al., 2009) and 6 h after CLP-induced sepsis (Mei et al., 2010) whereas, in our study, BMDMCs were injected 1 h after sepsis induction. Recently, Toya et al. (2011) showed that progenitor cells derived from human embryonic stem cells ameliorated

sepsis-induced lung inflammation Bumetanide and reduced mortality, though these cells did not change the production of IL-10. Thus, not only the moment of cell administration, but also the cell type may contribute to different anti-inflammatory responses. The administration of BMDMC therapy early in the course of the injury yielded a more favourable cytokine profile in the lung, contributing to an efficient control of the inflammatory injury, reducing the amount of alveolar collapse and preventing static lung elastance changes. Collagen fibre content increased at day 1 in the CLP-SAL group, which may be attributed to the higher degree of alveolar epithelial (Dos Santos, 2008 and Rocco et al., 2009) and endothelial lesion (Chao et al., 2010), as well as increased expression of TGF-β, PDGF, and HGF. These growth factors influence mesenchymal cell migration, extracellular matrix deposition (Adamson et al., 1988, Dos Santos, 2008 and Rocco et al., 2009) and epithelial repair.