Helicobacter pylori infection is associated with increased expression of macrophage migration inhibitory factor by T cells and macrophages in gastric mucosa

AIM Macrophage migration inhibitory factor (MIF) plays a pivotal role in inflammatory/immune diseases.This study aimed to determine MIF expression in H.pylori-induced gastritis,and the effect of H.pylori on MIF expression in monocytes in vitro.METHODS Seventy-nine patients (M/F,39/40,mean age,52 yrs) referred for upper endoscopy were selected;19 with gastric ulcer,15 with duodenal ulcer and 45 with non-ulcer dyspepsia (NUD).Gastric antral and body biopsies were obtained for histological examinations,double immunostaining for MIF/T-cells (CD45RO) and MIF/macrophage (KP1),and in situ hybridization for the expression of MIF mRNA.THp-1,a monocyte cell line,was co-incubated with different concentrations of the whole cell proteins prepared from H.pylori strain ATCC26695 or its isogenic type with cagA gene deleted.The expression of MIF protein was determined by using enzyme linked immunosorbent assay and the MIF mRNA by retrospective transcription-polymerase chain reaction techniques.RESULTS H.pylori was detected in 50 patients (10 with gastric ulcer, 15 with duodenal ulcer and 25 with NUD).Overall,the numbers of total T-cells,MIF+T-cells,total macrophages,MIF+macrophages and MIF mRNA+ cells were greater in the gastric antrum than in the body.There was a significant increase in the numbers of total T-cells, MIF+ T-cells,total macrophages,MIF+macrophages and MIF mRNA+cells in H. pylori positive,compared with H.pylori negative patients,in both the antral and body mucosa.Moreover,the cell numbers increased with more severe chronic gastritis in both the antrum and body.The numbers were also significantly higher in ulcer patients than in NUD patients, particularly in H. pylori positive patients.In vitro,the expression of MIF protein and mRNA in monocytes was significantly increased by incubation with H.pylori whole cell proteins,in a time and dose dependent manner.CONCLUSIONS H.pylori infection stimulates the expression of MIF in the gastric inflammatory cells,which may play a significance role in gastric inflammation and ulceration.

雷公藤内酯醇对内毒素激活小鼠腹腔巨噬细胞分泌促炎症介质NO和IL-6的影响

Objective Tripterygium wilfordii Hook. f. has been used for centuries in traditional Chinese medicine to treat autoimmune disease associated with increased production of the pro-inflammatory cytokine. Triptolide( TP) is a compound originally purified from T. wilfordii Hook f. and it has potent anti- inflammatory and immunosuppressant activities. In this study, we investigated the effect of TP on secretion of NO and IL-6 in celiac macrophages ( MΦ) activated by lipopolysaccharide ( LPS) in Kunming mice. Methods Celiac MΦ of mice were separated, purified, and activated by LPS, then cultured in vitro with TP of different concentrations. The level of NO in cellular supematants was determined by Griess reagent, and that of IL-6 was determined by ELISA. Results We found that pro-inflammatory cytokine NO activity in MΦ induced by LPS was significantly inhibited by TP ( 10-3-10 μg/ml) from 4-24 h in a time and dose- dependent manner (P < 0. 01). The level of IL-6 in MΦ was significantly inhibited by TP (10-3-10 μg/ml) at 12 h in a dose-dependent manner (P <0. 01). Conclusions We demonstrated that TP can inhibit levels of NO and IL-6 in celiac MΦ of Kunming mice activated by LPS.

Management of granulomatous mastitis

Granulomatous mastitis can be a disturbing disease. More patients have been affected in recent years. Clinicians need to understand the etiology and course of disease before they can formulate a useful treatment strategy. This paper aims to review the literature and the local experience on the management of the disease.

In addition to its lipid-lowering effect, atorvastatin exerts anti-inflammatory and antioxidant effects as well. In this study, we hypothesized that atorvastatin could protect against cerebral isch-emia/reperfusion injury. The middle cerebral artery ischemia/reperfusion model was established, and atorvastatin, 6.5 mg/kg, was administered by gavage. We found that, after cerebral ischemia/reperfusion injury, levels of the inflammation-related factors E-selectin and myeloperoxidase were upregulated, the oxidative stress-related marker malondialdehyde was increased, and super-oxide dismutase activity was decreased in the ischemic cerebral cortex. Atorvastatin pretreatment signiifcantly inhibited these changes. Our ifndings indicate that atorvastatin protects against ce-rebral ischemia/reperfusion injury through anti-inlfammatory and antioxidant effects.

The accumulation of myelin debris may be a major contributor to the inlfammatory response after diffuse axonal injury. In this study, we examined the accumulation and clearance of myelin debris in a rat model of diffuse axonal injury. Oil Red O staining was performed on sections from the cerebral cortex, hippocampus and brain stem to identify the myelin debris. Seven days after diffuse axonal injury, many Oil Red O-stained particles were observed in the cerebral cortex, hippocampus and brain stem. In the cerebral cortex and hippocampus, the amount of myelin debris peaked at 14 days after injury, and decreased signiifcantly at 28 days. In the brain stem, the amount of myelin debris peaked at 7 days after injury, and decreased signiifcantly at 14 and 28 days. In the cortex and hippocampus, some myelin debris could still be observed at 28 days after diffuse axonal injury. Our ifndings suggest that myelin debris may persist in the rat central ner-vous system after diffuse axonal injury, which would hinder recovery.

It is difficult to control the degree of ischemic postconditioning in the brain and other isch-emia-sensitive organs. Remote ischemic postconditioning could protect some ischemia-sensitive organs through measures on terminal organs. In this study, a focal cerebral ischemia-reperfusion injury model was established using three cycles of remote ischemic postconditioning, each cycle consisted of 10-minute occlusion of the femoral artery and 10-minute opening. The results showed that, remote ischemic postconditioning signiifcantly decreased the percentage of the in-farct area and attenuated brain edema. In addition, inlfammatory nuclear factor-κB expression was signiifcantly lower, while anti-apoptotic Bcl-2 expression was signiifcantly elevated in the ce-rebral cortex on the ischemic side. Our ifndings indicate that remote ischemic postconditioning attenuates focal cerebral ischemia/reperfusion injury, and that the neuroprotective mechanism is mediated by an anti-apoptotic effect and reduction of the inlfammatory response.

Glial cells in the central nervous system (CNS) contribute to formation of the extracellular matrix, which provides adhesive sites, signaling molecules, and a diffusion barrier to enhance efifcient neurotransmission and axon potential propagation. In the normal adult CNS, the extracellular matrix (ECM) is relatively stable except in selected regions characterized by dynamic remodel-ing. However, after trauma such as a spinal cord injury or cortical contusion, the lesion epicenter becomes a focus of acute neuroinlfammation. The activation of the surrounding glial cells leads to a dramatic change in the composition of the ECM at the edges of the lesion, creating a perile-sion environment dominated by growth inhibitory molecules and restoration of the peripheral/central nervous system border. An advantage of this response is to limit the invasion of damaging cells and diffusion of toxic molecules into the spared tissue regions, but this occurs at the cost of inhibiting migration of endogenous repair cells and preventing axonal regrowth. The following review was prepared by reading and discussing over 200 research articles in the ifeld published in PubMed and selecting those with signiifcant impact and/or controversial points. This article highlights structural and functional features of the normal adult CNS ECM and then focuses on the reactions of glial cells and changes in the perilesion border that occur following spinal cord or contusive brain injury. Current research strategies directed at modifying the inhibitory perile-sion microenvironment without eliminating the protective functions of glial cell activation are discussed.

Interleukin-18 gene promoter polymorphisms are potential risk factors for ischemic cerebrovascular disease, and the-607C al ele may increase ischemic stroke risk in the Han Chinese population. In the present study, we recruited 291 patients with ischemic cerebrovascular disease from the Affi-liated Hospital of Qingdao University Medical Col ege, China, and 226 healthy controls. Both pa-tients and controls were from the Han population in northern China. Immunoresonance scattering assays detected increased serum amyloid A protein, C-reactive protein, and interleukin-18 levels in ischemic cerebrovascular disease patients compared with healthy controls. Analysis of the-607C/A (rs1946518) polymorphism in the interleukin-18 gene promoter showed ischemic cerebrovascular disease patients exhibited increased frequencies of the CC genotype and C al eles than healthy controls. Genotype and al ele frequencies of the interleukin-18-137G/C (rs187238) polymorphism and the-13T/C (rs11024595) polymorphism in the 5'-flanking region of serum amyloid A, showed no significant difference between the two groups. Multivariate logistic regression analysis on the interleukin-18 promoter A/C genetic locus, for correction of age, gender, history of smoking, hyper-tension, diabetes mel itus, hypercholesteremia, and an ischemic stroke family history, showed ischemic cerebrovascular disease risk in individuals without the A al ele (C homozygotes) was 2.2-fold greater than in A al ele carriers. Overal , our findings suggest that the-13T/C (rs11024595) polymorphism in the 5′-flanking region of serum amyloid A has no correlation with ischemic cere-brovascular disease, but the C al ele of the-607C/A (rs1946518) polymorphism in the interleukin-18 promoter is a high-risk factor for ischemic cerebrovascular disease in the Han population of northern China. In addition, the A al ele is likely a protective gene for ischemic cerebrovascular disease.

Three-month-old Alzheimer’s disease model transgenic mice were immunized with Aβ1-42, Plp-Adenovirus [Ad]-X-CMV-(Aβ3-10)10-CpG [AdCpG-(Aβ3-10)10] or AdCpG virus lfuid via na-sal mucosal inhalation, respectively. ELISA analysis of serum showed Aβ42 antibody titers were signiifcantly increased in mice immunized with Aβ1-42 and AdCpG-(Aβ3-10)10. Concanavalin A and AdCpG-(Aβ3-10)10 stimulation signiifcantly increased the number of proliferating spleen cells cultured from AdCpG(Aβ3-10)10 and Aβ42 groups compared with the control group. In the AdCp-G(Aβ3-10)10 group, levels of interleukin (IL)-4 and IL-10 were increased, while those of IL-2 and interferon-γwere decreased. In the Aβ42 group, levels of IL-4, IL-10, IL-2 and interferon-γwere all increased. Experimental ifndings indicate that AdCpG-(Aβ3-10)10 vaccine can produce strong T helper 2 (hT2) humoral immune responses in addition to the production of Aβ42 antibody. hTe cellular immunologic response was weak and avoided Aβ1-42-mediated cytotoxicity.

选择性肺叶通气对肺功能不全患者开胸术中肺内分流及炎性反应的影响

Objective To investigate the effects of selective lobar ventilation on intrapulmonary shunt and inflammatory response in patients with pulmonary dysfunction during thoracotomy.Methods Thirty-four ASA Ⅱ or Ⅲ patients,aged 64-79 years,weighing 50-85 kg,with moderate or severe impaired pulmonary function,scheduled for esophageal cancer radical correction,were randomly divided into two groups (n =17 each):one-lung ventilation group (group A) and selective lobar ventilation group (group B).In group A,an endobronchial blocker tube was used to obstruct the bronchus principalis and practice one-lung ventilation.In group B,an endobronchial blocker tube was used to obstruct the bronchi Iobares and practice selective lobar ventilation.Blood samples were taken from the arteria radialis and the internal jugular vein for blood gas analysis and determination of plasma concentrations of tumor necrosis factor-alpha (TNF-α),interleukin-6 (IL-6) and IL-8 by enzyme linked immunosorbent assay (ELISA) before anesthesia induction (T0),30 minutes following two-lung ventilation at the lateral position (T1),60 minutes following one-lung ventilation or selective lobar ventilation (T2) and at the end of surgery (T3).Peak airway pressure (Ppeak) and plateau airway pressure (Pplat) were recorded at the same time.Results The incidence of hypoxemia was significantly lower in group B (0) than in group A (18％,P ＜ 0.05).Compared with group A,Pliat and Ppeak at T1-3,the intrapulmonary shunt rate (Qs/Qt) at T2,TNF-α,IL-6 and IL-8 concentrations at T2-3 were significantly decreased in group B (P ＜ 0.05).Conclusion Selective lobar ventilation can reduce intrapulmonary shunt and inhibit inflammatory responses to help lessen mechanical ventilation-related lung injuryduring thoracotomy in patients with pulmonary dysfunction.

雾化吸入小剂量氨溴索对开胸食道手术患者单肺通气时炎性反应的影响

Objective To investigate the effects of inhaled aerosolized low dose ambroxol on the inflammatory response to one-lung ventilation (OLV) in patients undergoing open-chest esophagus surgery.Methods Sixty patients (aged 39-64 years,weighing 50-85 kg and with height of 153-181 cm) with normal heart and lung function undergoing open-chest esophagus surgery were randomly divided into three groups:20 patients receiving intravenous infusion of normal saline (control group,group C),20 receiving intravenous infusion of ambroxol 10 mg/kg after induction of anesthesia (group IA) and 20 inhaling aerosolized ambroxol 30 mg after induction of anesthesia (group AIA).Arterial blood samples were taken after induction of anesthesia before ambroxol administration (T0,baseline),after 90 minutes of OLV (T1) and at 30 minutes after OLV (T2) for determination of plasma concentrations of tumor necrosis factor-alpha (TNF-α),interleukin-1 beta (IL-1β),IL-8 and IL-10 by enzyme linked immunosorbent assay (ELISA).Results The levels of TNF-α,IL-1β,and IL-8 in plasma significantly increased while the level of IL-10 in plasma significantly decreased at T1 and T2 as compared with the baseline at T0 in all the three groups.The levels of TNF-α,IL-1β,and IL-8 in plasma were significantly lower and the level of IL-10 in plasma was significantly higher at T1 and T2 in groups IA and AIA than in group C.Conclusion Both intravenous injection of large dose ambroxol and inhaled aerosolized low dose ambroxol can inhibit the inflammatory response to OLV in patients undergoing open-chest esophagus surgery.

滤除白细胞自体回收血对围术期患者红细胞免疫功能及全身炎症反应的影响

Objective To investigate the effect of leukocyte-depleted intraoperative salvaged blood on the erythrocyte immunity and systemic inflammatory response during the perioperative period in patients.Methods Twenty ASA Ⅰ or Ⅱ patients (aged 20-44 years and weighing 40-75 kg) requiring blood salvage during operation (with the estimated intraoperative blood loss of 15-20 ml/kg) were randomly divided into two groups (n =10 each):control group (group C) and leukocyte depletion group (group D).Anesthesia was induced with midazolam,fentanyl,propofol and vecuronium and maintained with isoflurane inhalation and intravenous infusion of propofol and remifentanil.The patients were mechanically ventilated after endotracheal intubation.Intraoperative blood salvage and reinfusion were performed in all the patients.In group D,the salvaged blood was filtered by a leukocyte depletion filter placed in the line of the reinfusion circuit.Blood samples were collected from the central vein before anesthesia (T1),at the end of surgery (T2) and 12 hours (T3) and 36 hours (T4) after operation in all the patients.The rosette rates of red blood cell-C3b receptors (RBC-C3bRR) and RBC-immune complex (RBC-ICR) were determined.The number of leukocytes and polymorphonuclear neutrophils (PMNs) were counted.The plasma levels of interieukin-6 (IL-6),tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) were measured,too.Results Compared with group C,the plasma levels of IL-6,TNF-α and MDA were significantly lower at T2-T4,the RBC-C3bRR was significantly higher at T3-T4 (P ＜ 0.01),and the number of PMNs was significantly lower at T4 in group D(P＜0.05).Conclusion Leukocyte-depleted intraoperative salvaged blood is helpful to improve the erythrocyte immunity during the perioperative period in patients,and the decrease of systemic inflammatory response may be involved in the mechanism.

The influence of autophagy on mouse inflammatory responses caused by Salmonella enterica serovar Typhimurium with spv genes

An investigation into the effects of Salmonella plasmid virulence genes (spv) on autophagy,apoptosis,and inflammation was carried out in mice,using a strain of Salmonella enterica serovar Typhimurium (S.typhimurium) SR-11 carrying spv.Strain BRD509 without spy was used as a control.Results showed that the expression of autophagy protein Beclin-1 in the livers and spleens in the SR-11 group was lower than that in the BRD509 group,while the apoptosis protein,Caspase-3,was higher in the SR-11 group.Inflammatory cytokine levels [interleukin 12 (IL-12) and interferon γ (IFN-γ)] were higher in the SR-11 group compared with those in the BRD509 group since 4 d post-infection.In addition,we found an increase in severe pathological changes and larger viable bacterial amounts in livers and spleens in the SR-11 group.After intervention with autophagy agonist rapamycin (RAPA),Beclin-1 expression increased in both groups,while Caspase-3 expression was different between the two groups: Caspase-3 decreased in the SR-11 group but increased in the BRD509 group.Moreover,RAPA decreased cytokine levels,bacterial quantity and organ-related injury in the SR-11 group whereas RAPA increased cytokine levels and aggravated organ injury in the BRD509 group.Results from these studies suggest that S.typhimurium with spv genes may exacerbate infection by inhibiting autophagy and affecting the production of inflammatory cytokines.RAPA-enhanced autophagy may improve the secretion of cytokines in order to protect the host from damaging by Salmonella infection.Our study suggests that the regulation of cellular autophagy may play a role in the prevention and control of certain infectious diseases.

Molecular Basis Linking Platelet to Inflammation

Introduction Blood platelets not only play an important role in hemostasis and thrombosis,but increasing evidence show that they participate in the induction of inflammation.Firstly,platelets contain and release cytokines and immune mediators.And platelets are able to modulate and regulate the function of surrounding cells by adhesion molecules or by the release of various factors.

Inflammation and Arterothrombosis

Arterial thrombosis is a central pathologic mechanism contributing to myocardial infarction and stroke, together the leading causes of death in China and developed countries.

Cell death plays an important role in the regulation of inflammation and may be the result of inflammation. The maintenance of tissue homeostasis necessitates both the recognition and removal of invading microbial pathogens as well as the clearance of dying cells. In the past few decades, emerging knowledge on cell death and inflammation has enriched our molecular understanding of the signaling pathways that mediate various programs of cell death and multiple types of inflammatory responses. This review provides an overview of the major types of cell death related to inflammation. Modification of cell death pathways is likely to be a logical therapeutic target for inflammatory diseases.

Objective:To detect serum chemokine RANTES content in patients with acute coronary syndrome and analyze its relationship with degree of inflammation and myocardial injury. Methods:116 cases of acute coronary syndrome (ACS) patients treated in our hospital from July 2012 to July 2014 were chosen as study group and divided into low-risk group (48 cases), moderate-risk group (33 cases) and high-risk group (35 cases) according to risk stratification; 109 cases of healthy people receiving physical examination during the same period were enrolled in healthy control group. Serum RANTES contents as well as levels of inflammatory cytokines and myocardial injury indicators in all groups were compared and the correlation was further analyzed.Results:Serum RANTES contents as well as levels of inflammatory factors and myocardial injury markers in ACS patients were all significantly higher than those in control group (P<0.05), and with the increase of coronary risk stratification, serum RANTES contents as well as levels of inflammatory factors and myocardial injury markers further rose (P<0.05); serum RANTES contents in ACS patients were positively correlated with levels of inflammatory cytokines and myocardial injury indicators.Conclusion: Increased levels of serum RANTES is one of the important factors contributing to the occurrence of ACS; it is positively correlated with levels of inflammatory cytokines and severity of myocardial injury in patients, and can guide clinical treatment and judge prognosis.