Goat anti Human TREM1 polyclonal antibody

Investigating the relationships between critical influenza viral mutations contributing to increased virulence and host expression factors will shed light on the process of severe pathogenesis from the systems biology perspective. We previously generated a mouse-adapted, highly virulent influenza (HVI) virus through serial lung-to-lung passaging of a human influenza H3N2 virus strain that causes low virulent influenza (LVI) in murine lungs. This HVI virus is characterized by enhanced replication kinetics, severe lung injury, and systemic spread to major organs. Our gene microarray investigations compared the host transcriptomic responses of murine lungs to LVI virus and its HVI descendant at 12, 48, and 96 h following infection. More intense expression of genes associated with cytokine activity, type 1 interferon response, and apoptosis was evident in HVI at all time-points. We highlighted dysregulation of the TREM1 signaling pathway (an amplifier of cytokine production) that is likely to be upregulated in infiltrating neutrophils in HVI-infected lungs. The cytokine gene expression changes were corroborated by elevated levels of multiple cytokine and chemokine proteins in the bronchoalveolar lavage fluid of infected mice, especially at 12 h post-infection. Concomitantly, the downregulation of genes that mediate proliferative, developmental, and metabolic processes likely contributed to the lethality of HVI as well as lack of lung repair. Overall, our comparative transcriptomic study provided insights into key host factors that influence the dynamics, pathogenesis, and outcome of severe influenza.

Herein, we found that serum concentration of superoxide dismutase 3 (SOD3) was significantly reduced in children with mycoplasma pneumonia (MP) infection. To study the roles of SOD3 in inflammatory regulation of MP infection, human A549 type II alveolar epithelial cells were stimulated with 10(7)CCU/ml of MP to build MP infectionin vitro. Secretion of pro-inflammatory cytokine interleukin (IL)-8 and tumor necrosis factor (TNF)-alpha were measured via enzyme-linked immunosorbent assay (ELISA) to assess the inflammatory response of A549 cells. Levofloxacin (LVFX) was used as an anti-inflammatory drug while recombinant TNF-alpha was used as an inflammatory promotor in MP-infected cells. Transcriptional activity of nuclear factor (NF)-kB was assessed by detecting protein levels of nuclear NF-kB and cytoplasm NF-kB using Western blot analysis. Our data suggested that the expression of SOD3 mRNA and protein, as well as content of SOD3 in cultured supernatant, were time-dependently inhibited in MP-infected A549 cells. However, lentiviruses-mediated SOD3 overexpression alleviated inflammatory response of MP-infected A549 cells, and prevented the unclear translocation of NF-kB, as evidenced by obviously reducing the production of IL-8 and TNF-alpha in cell cultured supernatant, as well as decreasing nuclear NF-kB while increasing cytoplasm NF-kB. Inspiringly, SOD3 overexpression induced anti-inflammatory effect and the inactivation of NF-kB was similar to that of 2 mu g/ml of LVFX, but reversed by additional TNF-alpha treatment. Therefore, we can conclude that transcriptional activity of NF-kappa B was the underlying mechanism, by which SOD3 regulated inflammatory response in MP infectionin vitro.