Endotoxemia and Specific Antibody Behavior against Different Endotoxins following Multiple Injuries

Hiki, Naoki; Berger, D.; Buttenschoen, Klaus; Boelke, E.; Seidelmann, M.; Strecker, W.; Kinzl, L.; Beger, Hans G.

doi:10.1097/00005373-199505000-00020

Cited by 37 publications

(29 citation statements)

References 29 publications

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“…The translocated lipopolysaccharide (LPS) from the gut (Hiki et al, 1995;Buttenschoen et al, 2000) has been indicated to potently trigger the inflammatory response to trauma, including bone fracture (Tobias et al, 1997); it has also been identified as a major bacterial deregulator in the activity imbalance of osteoblasts and osteoclasts (Nair et al, 1996). Thus, the effect of LPS on bone metabolism is therefore conceived to pose a clinical challenge to bone healing, particularly for trauma followed by endotoxinemia/sepsis.…”

Section: Introductionmentioning

confidence: 99%

miR-23b targets Smad 3 and ameliorates the LPS-inhibited osteogenic differentiation in preosteoblast MC3T3-E1 cells

Liu

Wang

et al. 2016

J. Toxicol. Sci.

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-Lipopolysaccharide (LPS) has been confirmed to be the main inhibitor in osteogenic differentiation, posing a clinical challenge to bone healing, particularly for trauma followed by endotoxinemia/sepsis. However, the molecular mechanism remains ambiguous. miR-23b, which regulates multiple signaling pathways in inflammation, has been shown to be deregulated by LPS. In this study, we examined the LPS-mediated regulation on the expression of miR-23b and Smad 3 in preosteoblast MC3T3-E1 cells. Then we determined the regulation of miR-23b overexpression on the Smad 3 expression and on the LPS-mediated inhibition of bone morphogenetic protein-2 (BMP-2)-induced osteogenic differentiation. Our results demonstrated that LPS significantly downregulated the expression of miR-23b, while upregulating Smad 3 in MC3T3-E1 cells. However, the transfection with miR-23b mimics markedly downregulated the Smad 3 in both mRNA and protein levels, via the specific binding to the 3'-untranslated region (UTR) of Smad 3. Moreover, though LPS markedly downregulated the BMP-2-induced osteogenic differentiation of MC3T3-E1 cells by inhibiting the expression of alkaline phosphatase (ALP), Osteocalcin (OCN), Osteopontin (OPN) and Runt-related transcription factor 2 (RUNX2). The upregulated miR-23b reversed such downregulation of ALP, OCN, OPN and RUNX2 in the MC3T3-E1 cells which were treated both with LPS and BMP-2. In conclusion, our data indicates that miR-23b ameliorates the LPS-mediated inhibition of BMP-2-induced osteogenic differentiation in MC3T3-E1 cells, implying the protective role of miR-23b in the LPS-mediated inhibition of osteogenic differentiation and bone formation.

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Section: Introductionmentioning

confidence: 99%

miR-23b targets Smad 3 and ameliorates the LPS-inhibited osteogenic differentiation in preosteoblast MC3T3-E1 cells

Liu

Wang

et al. 2016

J. Toxicol. Sci.

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“…Several studies showed significant endotoxemia after cardiac and general surgical procedures and after multiple injury [22][23][24][25][26][27][28]. The origin of the endotoxin reaching the cir culation was presumed to be the gastrointesti nal tract.…”

Section: Introductionmentioning

confidence: 99%

Determination of Endotoxin-Neutralizing Capacity of Plasma in Postsurgical Patients

et al. 1996

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In 92 patients who underwent abdominal and goiter surgery endotoxin and endotoxin-neutralizing capacity (ENC) were determined in plasma preoperatively and daily postoperatively. Endotoxin plasma levels started to increase on day 1 in patients who were laparotomized. Correspondingly ENC was reduced during the 1st postoperative week. Even on the 1st postoperative day determination of ENC made the differentiation between patients possible who showed an uneventful course and patients who developed pneumonia, pulmonary failure, or mental disorders. Furthermore the need for diuretics in order to maintain sufficient renal function was associated with lower ENC during days 1–3. Endotoxin plasma levels were significantly elevated in patients who developed pneumonia during days 1–4, whereas the occurrence of pulmonary failure was only correlated with elevated endotoxin levels on day 3. Endotoxemia was pronounced in patients needing diuretics on days 1, 4, and 5. In patients who underwent goiter surgery ENC changed significantly as found for endotoxin plasma values during the postoperative course. Determination of endotoxin and especially ENC with the use of the limulus amebocyte lysate test turned out to be a reliable method correlating with impending complications at least in postsurgical patients.

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“…Inflammation is a likely feature of bone repair processes, and several cytokines have been reported to be involved in bone metabolism (Girasole et al 1994, Einhorn et al 1995, Lader and Flanagan 1998, Ueda et al 1998, Ohlin et al 1999, Suda et al 1999. Experimental and clinical experience indicates that trauma causes translocation of lipopolysaccharide (LPS) endotoxin from the gut (Hiki et al 1995, Buttenschoen et al 2000. LPS is a potent trigger of the mediator cascade and the inflammatory response (Tobia et al 1997), and it has been identified as a major bacterial bone resorbing factor (Nair et al 1996).…”

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confidence: 99%

Lipopolysaccharide impairs fracture healing: An experimental study in rats

et al. 2005

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Background It has been shown that trauma causes translocation of lipopolysaccharide (LPS) endotoxins from the gut. LPS has been identified as a major bacterial bone resorbing factor. The effects of LPS on bone healing are therefore of clinical interest, as trauma involving fractures followed by sepsis is a clinical scenario. We investigated the effects of systemic and local administration of LPS on the healing of femoral fractures in rats.Animals and methods In 3 groups, each consisting of 9 rats, a mid-diaphyseal osteotomy/fracture of the femoral bone was performed and then nailed. In one group of animals, LPS was applied intraperitoneally (systemically), and in another group, LPS was applied locally at the fracture site. The third group served as a control. The animals were killed after 6 weeks, and the mechanical characteristics of the healing osteotomies were evaluated.Results We found that LPS induced a hypertrophic and immature callus, as evaluated by bone mineral content and density. In the rats given LPS intraperitoneally, the mechanical strength characteristics were reduced, as evaluated by bending moment, rigidity, and energy absorption.Interpretation The rats given LPS intraperitoneally reflect a clinical situation with fracture trauma and endotoxinemia. Our findings indicate that endotoxinemia may impair the fracture healing processes.

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Endotoxemia and Specific Antibody Behavior against Different Endotoxins following Multiple Injuries

Cited by 37 publications

References 29 publications

miR-23b targets Smad 3 and ameliorates the LPS-inhibited osteogenic differentiation in preosteoblast MC3T3-E1 cells

miR-23b targets Smad 3 and ameliorates the LPS-inhibited osteogenic differentiation in preosteoblast MC3T3-E1 cells

Determination of Endotoxin-Neutralizing Capacity of Plasma in Postsurgical Patients

Lipopolysaccharide impairs fracture healing: An experimental study in rats

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