Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular endothelium is a major target for the inflammatory damage that occurs with multiple organ dysfunction associated with sepsis and other trauma. The growing appreciation of endothelium as a target of inflammation has obscured the importance of these cells as a source of inflammatory mediators. In the following study we evaluated the ability of tumor necrosis factor-alpha (TNF) to induce the synthesis of complement component C3 in human umbilical vein endothelial cells (HUVEC) and whether pentoxifylline (PTX) could reduce C3 expression. Confluent monolayers of HUVEC were treated with increasing concentrations of TNF with and without two concentrations of PTX. Concentrations of C3 were determined every 48 h for 144 h in cellular supernatants and C3 mRNA was amplified using RT-PCR. TNF increased C3 release from HUVEC in a concentration dependent manner. PTX added at the same time as TNF significantly reduced C3 release at the 96 h time point. Consistent with data on C3 release PTX inhibited the increased C3 mRNA expression associated with TNF treatment. TNF increases C3 synthesis and release from endothelial cells which were inhibited by clinical concentrations of PTX. This data further supports the potential benefit of PTX in multiple organ dysfunction and other inflammatory processes involving the endothelium by inhibiting one of the major mediators of vascular damage.
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PMID:Pentoxifylline inhibits tumor necrosis factor-alpha induced synthesis of complement component C3 in human endothelial cells. 1546 17

A viral hemorrhagic septicemia virus (VHSV), recombinant glycoprotein vaccine (VHSVg) and a DNA vaccine (pCMV-VHSg) were injected in Japanese flounder (Paralichthys olivaceus). Each fish was injected with 10 microg vaccine dissolved in 50 microl phosphate buffer saline (PBS). One month after the vaccination, the fish were challenged intraperitoneally with either 1 x 10(2) or 1 x 10(3) TCID(50) of virus. Fish that received the VHSg DNA vaccine were highly protected against virus infection over a 21-day observation period, with cumulative mortalities ranging from 4 to 10%. However, the recombinant protein vaccine group appeared to have low survival rates. Using microarray analysis, humoral defense-related genes such as complement component C3, complement regulatory plasma proteins, IgM, IgD, MHC class II-associated invariant chain and CD20 receptor were observed to be up-regulated by the VHSg recombinant protein vaccine at 1 or 21 days post vaccination. On the other hand, cellular defense-related genes such as CD8 alpha chain, T-cell immune regulator, MIP1-alpha and apoptosis-associated protein were not detected. Specific antibodies against VHSVg protein were detected in both vaccinated groups at a titer of 1:40 at 28 days post vaccination.
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PMID:Comparative immune responses in Japanese flounder, Paralichthys olivaceus after vaccination with viral hemorrhagic septicemia virus (VHSV) recombinant glycoprotein and DNA vaccine using a microarray analysis. 1618 91

Streptococcus suis serotype 2 (S. suis 2)-induced sepsis and meningitis are often accompanied by bacteremia. The evasion of polymorphonuclear leukocyte-mediated phagocytic clearance is central to the establishment of bacteremia caused by S. suis 2 and is facilitated by the ability of factor H (FH)-binding protein (Fhb) to bind FH on the bacterial surface, thereby impeding alternative pathway complement activation and phagocytic clearance. Here, C3b/C3d was found to bind to Fhb, along with FH, forming a large immune complex. The formation of this immune complex was mediated by domain II of Fhb via electrostatic and hydrophobic interactions, which, to our knowledge, is a new type of interaction. Interestingly, Fhb was found to be associated with the cell envelope and also present in the culture supernatant, where secreted Fhb inhibited complement activation via interactions with domain II, thereby enhancing antiphagocytic clearance by polymorphonuclear leukocytes. Thus, Fhb is a multifunctional bacterial protein, which binds host complement component C3 as well as FH and interferes with innate immune recognition in a secret protein manner. S. suis 2 therefore appears to have developed a new strategy to combat host innate immunity and enhance survival in host blood.
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PMID:Mechanisms of Host-Pathogen Protein Complex Formation and Bacterial Immune Evasion of Streptococcus suis Protein Fhb. 2734 78


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