Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031154 (peritonitis)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mast cells play an important role in innate immunity as well as in allergic reaction. However, regulatory mechanisms underlying mast cell-mediated innate immune responses remain largely unknown. Here we determined whether Smad3, a major signal transducer of TGF-beta, regulates innate immune response by mast cells against Gram-negative bacteria. Bone marrow-derived mast cells (BMMC) obtained from Smad3 null mutant mice showed augmented capacity to produce proinflammatory cytokines upon stimulation with a Gram-negative bacteria-associated product, LPS. In acute septic peritonitis model induced by cecal ligation and puncture, mast cell-deficient W/W(v) mice reconstituted with Smad3 null BMMC had significantly higher survival rate than W/W(v) mice reconstituted with wild-type BMMC, which was associated with higher production of proinflammatory cytokines in the peritoneal cavity. These in vitro and in vivo results suggest that Smad3 in mast cells functions as inhibitory for mast cell-mediated innate immune response against Gram-negative bacteria. Suppression of Smad3 expression in mast cells may thus have therapeutic potential for Gram-negative bacterial infection such as acute septic peritonitis by augmenting innate immune responses of mast cells.
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PMID:Smad3 deficiency in mast cells provides efficient host protection against acute septic peritonitis. 1577 80

G-CSF is a hemopoietic growth factor involved in granulocytic differentiation of progenitor cells. In this study, we investigated the effects of PGE2 on G-CSF production in murine peritoneal neutrophils in vitro and in vivo. PGE2 augmented LPS-primed G-CSF release from peritoneal neutrophils. This augmentation was mimicked by a type E prostanoid receptor (EP)2-selective agonist but not by other EP-specific agonists. Indeed, the effect of PGE2 on G-CSF release was abolished in neutrophils isolated from EP2-deficient mice. PGE2 and an EP2 agonist have the ability to stimulate G-CSF gene expression even in the absence of LPS. In the casein-induced peritonitis model, the appearance of G-CSF in the casein-injected peritoneal cavity associated well with the timing of neutrophil infiltration as well as PGE2 levels in exudates, with a peak value at 6 h postinjection. Inhibition of endogenous PG synthesis by indomethacin resulted in a marked decrease in G-CSF content and neutrophil number in the peritoneal cavity. Moreover, EP2-deficient mice exhibited a strikingly reduced G-CSF content in peritoneal exudates with comparable responses in neutrophil migration and local PGE2 production at 6 h postinjection. These results suggest that the PGE2-EP2 system contributes to the local production of G-CSF during acute inflammation.
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PMID:Prostaglandin E2 stimulates granulocyte colony-stimulating factor production via the prostanoid EP2 receptor in mouse peritoneal neutrophils. 1608 35

An effective clearance of microbes is crucial in host defense during infection. In the present study, we demonstrate that CC chemokine receptor 8 (CCR8) skews innate immune response during septic peritonitis induced by cecal ligation and puncture (CLP). CCR8 was expressed in resident peritoneal macrophages and elicited leukocytes during CLP in the wild-type CCR8+/+ mice. CCR8-/- mice were resistant to CLP-induced lethality relative to CCR8+/+ mice, and this resistance was associated with an augmented bacterial clearance in CCR8-/- mice. In vitro, peritoneal macrophages from CCR8-/- mice, but not neutrophils, exhibited enhanced bactericidal activities relative to those from CCR8+/+ mice. Upon stimulation with the bacterial component LPS, elevated levels of superoxide generation, lysosomal enzyme release, and nitric oxide generation, effector molecules for bacterial killing were detected in CCR8-/- macrophages relative to CCR8+/+ macrophages. In addition, CCR8-/- macrophages produced significantly higher levels than CCR8+/+ macrophages of several cytokines and chemokines known to augment bactericidal activities of leukocytes that include TNF-alpha, IL-12, macrophage-derived chemokine (MDC/CCL22), macrophage inflammatory protein (MIP)-2, and KC. Altogether, these results indicate that CCR8 may have a negative impact on host defense during septic peritonitis, providing a new paradigm for the role of CCR8 in innate immunity.
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PMID:Absence of CC chemokine receptor 8 enhances innate immunity during septic peritonitis. 1638 13

Alcoholic liver disease (ALD) is a major public health problem in the United States and women are known to be more susceptible to ALD. However, the precise mechanism for increased susceptibility of females to ALD is not completely understood. The present study is based on the hypothesis that induction of osteopontin (OPN), a matricellular protein, is the likely contributing factor for higher neutrophil recruitment in females during alcoholic steatohepatitis (ASH). ASH was induced in male and female Sprague-Dawley rats by feeding them a Lieber-DeCarli diet containing ethanol (EtOH) for 6 weeks, followed by a single injection of lipopolysaccharide (LPS, 10 mg/kg, ip). Liver injury, measured by plasma transaminase elevations and confirmed by haematoxylin and eosin-stained liver sections, revealed approximately 25-fold higher liver injury in the female ASH model compared with the males. Although steatosis, necrosis, and neutrophil infiltration were evident in both male and female rats, hepatic neutrophilic necrotic foci were noted as early as 2 h after LPS injection in the EtOH-treated female rats. Hepatic neutrophil infiltration correlated with higher expression of cleaved (cOPN) and uncleaved OPN in the EtOH + LPS-treated female rats compared with the males. OPN secretion was localized predominantly in the biliary epithelium and females had significantly higher OPN mRNA than their male counterparts in the ASH model. The ability of OPN to attract neutrophils was further confirmed in vivo, in a peritonitis rat model, and by neutralizing OPN (nOPN) antibody experiments. Hepatic neutrophil infiltration was largely inhibited ( approximately 50%) by nOPN antibody. Flow cytometry experiments revealed OPN-mediated up-regulation of the CD11b neutrophil adhesion molecule. In conclusion, these data suggest that higher hepatic expression of OPN is the likely reason for higher and early hepatic neutrophil infiltration making females more susceptible to ALD during ASH.
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PMID:Higher neutrophil infiltration mediated by osteopontin is a likely contributing factor to the increased susceptibility of females to alcoholic liver disease. 1644 Feb 89

Matrix metalloproteinase (MMP)-9 is involved in extracellular matrix degradation and leukocyte migration. To determine the role of MMP-9 in the innate immune response to peritonitis, MMP-9 gene-deficient (MMP-9(-/-)) and normal wild-type mice were i.p. infected with Escherichia coli. MMP-9 mRNA and pro-MMP-9 protein levels increased rapidly upon induction of peritonitis. Although MMP-9(-/-) neutrophils showed a normal phagocytosis of E. coli in vitro, MMP-9(-/-) mice displayed a reduced resistance against E. coli peritonitis, as indicated by an enhanced bacterial outgrowth in the peritoneal cavity and increased dissemination of the infection. Furthermore, the cytokine response to LPS was not influenced by MMP-9 deficiency. However, during E. coli peritonitis, MMP-9(-/-) mice showed much higher peritoneal chemokine and cytokine levels compared with wild-type mice. Despite the increased local chemokine concentrations, MMP-9(-/-) mice displayed a diminished recruitment of leukocytes to the site of infection, indicating that cellular migration was impaired. Moreover, MMP-9(-/-) mice developed more severe distant organ damage during infection. These data suggest that MMP-9 is an essential component of an effective host response to E. coli peritonitis.
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PMID:Matrix metalloproteinase-9 deficiency impairs host defense against abdominal sepsis. 1651 42

To explore the effects of metronidazole (Me) on intestinal microcirculation in septic rats, intravital microscopy (IVM) following 16 hours of colon ascendens stent peritonitis (CASP model) was used. Four groups of animals were studied: control group (sham operation) and CASP group, each with and without Me treatment (10 mg/kg i.v.). In order to investigate the substance-specific effects of Me independently of the antibacterial effects within a pathologically altered microcirculation, a second experimental series with lipopolysaccharide challenge (LPS model) was carried out. The LPS model consisted of the four groups (control animals and LPS animals (15 mg/kg i.v. LPS from E. coli) with and without Me). IVM in the LPS experiments was performed following a two hour observation period. Me treated CASP or LPS animals, as compared with untreated, demonstrated significant improvement of functional capillary density (FCD) of the intestinal wall. The increase in the number of leukocytes firmly adhered to the endothelium (leukocyte sticking) in the untreated CASP or LPS animals within the V1 venules of the intestinal submucosal layer, was significantly reduced in the Me treated animals. In conclusion, Me exerts beneficial anti-bacterial and anti-inflammatory effects within the septic microcirculation.
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PMID:Metronidazole improves intestinal microcirculation in septic rats independently of bacterial burden. 1661 67

The effect of PACAP 38 administration on neuroendocrine and immune parameters was examined in rats with LPS-induced peritonitis. Treatment with PACAP 38 alone did not influence the serum level of the cytokines and hormones examined, but significantly decreased immune cell activity. When administered together with LPS, PACAP 38 reversed its effect on immune and humoral parameters, causing a decrease in the serum concentrations of TNFalpha and corticosterone, and an increase in T4 and GH. The majority of PACAP 38 effects disappeared earlier than those previously observed for VIP. PACAP 38 appears to represent a short-lasting modulator of immune and endocrine responses during acute inflammation.
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PMID:PACAP 38 as a modulator of immune and endocrine responses during LPS-induced acute inflammation in rats. 1680 97

Sepsis results in a state of relative immunosuppression, rendering critically ill patients susceptible to secondary infections and increased mortality. Monocytes isolated from septic patients and experimental animals display a "deactivated" phenotype, characterized by impaired inflammatory and antimicrobial responses, including hyporesponsiveness to LPS. We investigated the role of the LPS/TLR4 axis and its inhibitor, IL-1 receptor-associated kinase-M (IRAK-M), in modulating the immunosuppression of sepsis using a murine model of peritonitis-induced sepsis followed by secondary challenge by intratracheal Pseudomonasaeruginosa. Septic mice demonstrated impaired alveolar macrophage function and increased mortality when challenged with intratracheal Pseudomonas as compared with nonseptic controls. TLR2 and TLR4 expression was unchanged in the lung following sepsis, whereas levels of IRAK-M were upregulated. Macrophages from IRAK-M-deficient septic mice produced higher levels of proinflammatory cytokines ex vivo and greater costimulatory molecule expression in vivo as compared with those of their WT counterparts. Following sepsis and secondary intrapulmonary bacterial challenge, IRAK-M(-/-) animals had higher survival rates and improved bacterial clearance from lung and blood compared with WT mice. In addition, increased pulmonary chemokine and inflammatory cytokine production was observed in IRAK-M(-/-) animals, leading to enhanced neutrophil recruitment to airspaces. Collectively, these findings indicate that IRAK-M mediates critical aspects of innate immunity that result in an immunocompromised state during sepsis.
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PMID:Sepsis-induced suppression of lung innate immunity is mediated by IRAK-M. 1691 41

Frequently used experimental models of sepsis include cecal ligation and puncture, ascending colon stent peritonitis, and the i.p. or i.v. injection of bacteria or bacterial products (such as LPS). Many of these models mimic the pathophysiology of human sepsis. However, identification of mediators in animals, the blockade of which has been protective, has not translated into clinical efficacy in septic humans. We describe the shortcomings of the animal models and reasons why effective therapy for human sepsis cannot be derived readily from promising findings in animal sepsis.
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PMID:The disconnect between animal models of sepsis and human sepsis. 1702 Sep 29

In this study, in an animal model of zymosan-induced peritonitis we have tested anti-inflammatory properties of Taurolidine (TRD), a synthetic derivative of taurine. In vitro, the effect of TRD and HOCl treated TRD on peritoneal macrophages was compared with that of TauCl. We report that locally administered TRD (Taurolin) shows strong anti-inflammatory properties. TRD inhibits vascular permeability increased by inflammatory stimuli; it also significantly attenuates the influx of neutrophils into the peritoneal cavity, as well as the production of pro-inflammatory cytokines (TNF-alpha, IL-6) by peritoneal exudate cells. Chlorination of TRD resulted in the formation of chloramine (TRD-Cl), as confirmed by characteristic UV spectra. Both TRD and TRD-Cl, more effectively than TauCl, inhibited the production of IL-6 by stimulated macrophages. The effect was not dependent on its well-known anti-endotoxin activity since TRD inhibited cytokine production by macrophages stimulated with either LPS or IFN-gamma. Finally, we report that anti-inflammatory activities of TRD and taurine haloamines are mediated by different mechanisms. TRD, in contrast to TauCl and TauBr, does not induce expression of HO-1, a stress inducible enzyme with strong anti-inflammatory properties.
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PMID:Anti-inflammatory effects of taurine derivatives (taurine chloramine, taurine bromamine, and taurolidine) are mediated by different mechanisms. 1715 35


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