Models and Paradigms for Assessment of Antidepressant Effects
Scott Mendelson in Herbal Treatment of Major Depression, 2019
There are several methods by which the anti-inflammatory effects of herbs are evaluated. One of the most common techniques is to gauge the ability of substances to attenuate lipopolysaccharide-induced inflammation. The lipopolysaccharide can be administered to intact animals, or placed into cultured peripheral immune cells, microglia, or neuron-like pheochromocytoma cell lines. Lipopolysaccharide is a major molecular component of the outer membrane of gram-negative bacteria, and is the primary activator of the evolutionarily ancient innate immunity system. Lipopolysaccharide activates the toll-like receptor type4 (TLR4) that then initiates the intracellular inflammatory cascade. The translocation of NF-kβ to the nucleus enhances synthesis of the inflammatory cytokines TNF-α and IL-1β, as well as prostaglandins, leukotrienes, and Reduced Oxygen Species. In T-lymphocytes, NK cells and many other cell types, the release of IL-12 or IL-18 induces release of IFN-γ. The IFN-γ hypersensitizes mononuclear phagocytes to lipopolysaccharide, thus amplifying the inflammatory process.7 In some cases, the mechanism by which herbs interfere with the lipopolysaccharide-induced inflammatory cascade are explored, such as antagonism of TLR4, or prevention of translocation of NF-kβ. In most cases, the anti-inflammatory effects are established by assessing the degree to which the levels of the inflammatory cytokines are contained.
Urinary Tract Infection
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
The antigenic structure of the bacterial surface is classically described in terms of three classes of antigens. O-Antigens represent the polysaccharide side chains of the lipopolysaccharide structure found in all gram-negative bacteria. The polysaccharide is anchored to the outer membrane by lipid A (Fig. 18), the agent thought to be responsible for endotoxic shock, as described below. O-antigens are heat stable and classically certain serogroups (01, 02, 04, 06, 07, 016, 018, and 075) responsible for urinary infections, such strains being responsible for up to 80% of cases of pyelonephritis. Modern theory suggests that the O-antigen is not itself specifically responsible for pathogenicity; rather, the identified serogroups represent clones of organisms with a selection or panel of various virulence properties that enable successful colonization of the urinary tract. Other serogroups and hence other combinations of virulence factors may enable successful colonization of other areas such as the gastrointestinal tract. K capsular antigen is partially heat stable and may, on occasion, partially obscure the O-antigen (Fig. 18). K capsular polysaccharide antigen has been strongly associated with pyelonephritis for many years, both in adults (71) and in children (72). Some 70% of strains from children with pyelonephritis were associated with K1, K2, K3, K12, and K13 antigens, of which K1 is acknowledged to be the most frequently associated strain with pyelonephritic disease. Interestingly, K1 strains have also been associated with 80% of E. coli strains causing neonatal meningitis (72).
Chemical Structure of the Core Region of Lipopolysaccharides
Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison in Endotoxin in Health and Disease, 2020
Depending on the size of the saccharide portion, there exist two types of lipopolysaccharides (LPS), i.e., smooth- and rough-form (S- and R-form) LPS (1–3). Both consist of lipid A and, covalently linked to it, a saccharide portion composed of up to 15 sugars—the core region (3–5). In S-form LPS, this core region is replaced by the O-specific polysaccharide. Both LPS forms are found in wild-type gram-negative bacteria: the S-form, for example, in Escherichia coli, Klebsiella pneumoniae, Acinetobacter, or Vibrio cholerae, and the R-form in Neisseria meningitidis, N. gonorrhoeae, Haemophilus influenzae, and Bordetella pertussis. Mutants that are not able to synthesize a minimal core structure are not viable. Thus, the core region and lipid A represent a common structural unit occurring in all LPS, suggesting these components to be important for viability and membrane function. Herein, the chemical structure of the core regions of LPS is reviewed. Although part of the work was summarized recently (3–5), this review contains all structures presently known and the respective references.
Prospective study reveals a microbiome signature that predicts the occurrence of post-operative enterocolitis in Hirschsprung disease (HSCR) patients
Published in Gut Microbes, 2020
Weibing Tang, Yang Su, Chen Yuan, Yuqing Zhang, Lingling Zhou, Lei Peng, Pin Wang, Guanglin Chen, Yang Li, Hongxing Li, Zhengke Zhi, Hang Chang, Bo Hang, Jian-Hua Mao, Antoine M. Snijders, Yankai Xia
It is well known that lipopolysaccharide is produced by Gram-negative bacteria.29,30 We performed KEGG pathway analysis and found significant enrichment for LPS biosynthesis proteins and secretion system in postoperative HAEC cases. Significant enrichment for LPS biosynthesis proteins and secretion system was also observed in patients without exclusive breastfeeding. ELISA with the homogenate of the enteric tissue in the cutting edge of the dilated segment confirmed that the level of LPS was increased in postoperative HAEC cases and decreased in the exclusive-breastfeeding group. We found that Gram-negative bacteria belonging to the family Caulobacteraceae were most positively correlated with LPS levels. These data indicate that breastfeeding might decrease the abundance of microbes that produce LPS and potentially lower the risk of postoperative HAEC. A multi-center study to further validate this finding and explore the underlying mechanism is granted.
Deer antler based active ingredients have protective effects on LPS/d -GalN-induced acute liver injury in mice through MAPK and NF-κB signalling pathways
Published in Pharmaceutical Biology, 2022
Guixiang He, Quanmin Zhao, Yan Zhao, Ying Zong, Shigang Gu, Mengjie Li, Renjie Li, Jiaxin Sun
Macrophages are the most important immune cells and play a variety of immunomodulatory roles in various inflammatory diseases. Once activated, macrophages release a series of inflammatory cytokines (Fujiwara and Kobayashi 2005). Lipopolysaccharide is a cell wall component of Gram-negative bacteria, which interferes with the receptors of immune cells (Chen et al. 2018). Lipopolysaccharide is one of the most potent activators of mononuclear macrophages and is known to produce pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α and pro-inflammatory mediators, such as NO and PGE2 (Yang et al. 2012; Abarikwu 2014). Therefore, we selected mouse monocyte macrophages RAW 264.7 to screen the isolated and purified antler base protein extract, and found that the NO production of RAW264.7 cells after 4 h pre-treatment with R1 protein component was significantly reduced. We also measured the cytokines IL-6, IL-1β and TNF-α to further verify the anti-inflammatory effect of the R1 protein component. The results demonstrated that pre-treatment with R1 protein component, inflammatory factors were reduced in a dose-dependent manner. Therefore, we speculate that the R1 protein component of deer antler base may have a pre-protective effect on ALI through anti-inflammatory effects.
Macrophage membrane biomimetic drug delivery system: for inflammation targeted therapy
Published in Journal of Drug Targeting, 2023
Yulu Zhang, Yu Long, Jinyan Wan, Songyu Liu, Ai Shi, Dan Li, Shuang Yu, Xiaoqiu Li, Jing Wen, Jie Deng, Yin Ma, Nan Li
Bacterial infections are the most common type of infectious disease and can affect a wide range of organs and tissues, even causing sepsis and septic shock, and have serious public health consequences [98,99]. Endotoxin, also known as lipopolysaccharide (LPS), is an important pathogenic trigger for Gram-negative bacterial sepsis. It can reach target organs after circulation and cause lethal damage to the organism [100,101]. Effective removal of LPS is an important method for the successful treatment of bacterial infections and their complications. Macrophages are cells that can respond rapidly to microenvironmental signals. During bacterial infection, macrophages are among the first responders. Macrophages recognise pathogen-associated molecular patterns (PAMPs), such as LPS, through toll-like pattern recognition receptors on them [102]. LPS binding to macrophages activates TLR4 and activates transcription factors (e.g. interferon regulatory factors) and NF-κB to initiate inflammatory responses as a means of regulating bacterial phagocytic uptake and intracellular transport [103]. Therefore, the critical role played by macrophages and their surface receptors in LPS signalling provides new ideas for the treatment of bacterial infections and their complications.
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