Objective To investigate the effects and mechanisms of pentoxifylline ( PTX )pretreatment on acute lung injury ( ALI) induced by hemorrhagic shock in mice. Methods Ninety mice were randomly divided into three groups, ie. a control group, a hemorrhagic shock group, and a PTX group.Lung histological changes were examined by HE staining. Meanwhile, the wet-to-dry weight ratio ( W/D) and myeloperoxidase ( MPO) activity in lung were measured. The levels of TNF-αand IL-1βin lung homogenatewere measured by ELISA. The expressions of TLR4 mRNA and TLR4 protein in lung were detected by reverse transcription-polymerase chain reaction ( RT-PCR ) and Western blot, respectively. Results Hemorrhagic shock induced obvious ALI changes in lungs of the hemorrhagic shock group. W/D and MPO activity were significantly higher in the hemorrhagic shock group than the control group( P lt; 0. 01) . The expressions of TNF-α, IL-1β, TLR4 mRNA and TLR4 protein were also significantly higher than the control group( P lt;0. 01) . PTX pretreatment could relieve ALI changes induced by hemorrhagic shock, and decrease W/D and MPO activity. The expressions of TNF-α, IL-1β, TLR4 mRNA and TLR4 protein were also decreased by PTX pretreatment. Conclusions PTX pretreatment shows protective effects on ALI afterhemorrhagic shock. Its possible mechanismmay relate to down-regulation of TLR4, thus inhibit the expression of pro-inflammatory cytokins.
Abstract: Objective To investigate the phonetype and tolerogenic function of semimature dendritic cells (DC) transfected by myeloid differentiation marker 88（MyD88） small interfering ribonucleic acid（siRNA）. Methods Bone marrow of BALB/c mice was inoculated and cultured in vitro，and induced into DC by 10ng/ml recombinated granulocyte macrophage colony stimulating factor (rmGM-CSF) ，then DC was divided into three groups at the 8th day: blank control group: added nothing; lipopolysaccharide （LPS）group: added with 1μg/ml LPS; and experimental group: added with 1μg/ml LPS after transfected by MyD88 siRNA for 4 hours. The phonetype of three groups was analysed by fluorescenceactivated cell sorting (FACS). The concentration of interleukin 10（IL-10）and interleukin 12（IL-12） in culture supernatant was detected by enzyme linked immunosorbent assay（ELISA）.The function of stimulating alloreactive T cell roliferation were evaluated by primary and secondary mixed lymphocyte reaction （MLR）. The cardiac allograft survival time was compared after DC of three groups injected into recipient mice. Results The phonetype of blank control group DC was CD11c＋，CD25-，CD40low，CD80low，CD86low，MHC-Ⅱlow， which could be induced to mature DC by LPS. Experimental group DC was phonetypically semimature DC (CD11c＋，CD25－，CD40mid，CD80low，CD86low，MHC-IIid) and the IL-10/IL-12 ratio of semimature DC increases significantly. yporesponsiveness of alloactive T cells can be induced by experimental group DC and the survive time of heart allograft was prolonged. Conclusion Immature DC could become semimature DC after transfected by MyD88 siRNA and stimulation by LPS. These semimature DC are more tolerogenic than immature DC.
Objective To summarize the important role of myeloid differentiation factor 88 （MyD88） in toll like receptor （TLR） signaling pathway， and to summarize the relationship between MyD88 and relative diseases， and its potential application value. Methods Domestic and international publications online involving the role of MyD88 in TLR signaling pathway and the influence of MyD88 in some kinds of diseases in recent years were collected and reviewed. Results MyD88 was an important adapter protein， and played a connecting role in the TLR signaling pathway. It was the bottle neck of TLR signaling pathway， and could lead to the activation of many transcription factor to initiate innate immune response. It was also related to a variety of diseases. Conclusions MyD88 is the key adapter protein in TLR signaling pathway. It plays an important role in innate immunity， acquired immunity， and a variety of diseases， so it is a potential therapeutic target.
【Abstract】ObjectiveTo study Toll like receptor 4 (TLR4) expression on peripheral blood monocytes (PBMCs) during the early stage of human acute pancreatitis. MethodsThirty consecutive patients with acute pancreatitis admitted within 24 h of onset of abdominal pain were enrolled in this study. Another 20 healthy volunteers were included as control. Blood samples were collected by venipuncture on the day of admission and 3， 7 d after admission and PBMCs were isolated. TLR4 and CD14 expressions on PBMCs were detected by flow cytometry. Serum tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were measured simultaneously. Correlations between these parameters were analyzed. ResultsTLR4 expression increased on the day of admission and then continued to decline for several days. On third day, TLR4 expression was almost normal compared with the normal control. The alteration of serum TNF-α was consistent with that of TLR4. ConclusionDuring the early stage of human acute pancreatitis, mononuclear-macrophages may be ignited through TLR4 (a door keeper of innate immune system), which lead to TNF-α production.
ObjectiveTo systematically evaluate the association between Toll like receptor 2 (TLR2) gene I/D polymorphism and the risk of cancer. MethodsWe searched PubMed, EMbase, The Cochrane Library (Issue 7, 2015), CBM, CNKI, VIP and WanFang Data to collect case-control studies about the association between TLR2 gene I/D polymorphism and the risk of cancer from inception to July 2015. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was conducted using RevMan 5.3 software. ResultsA total of 11 case-control studies involving 3 250 cancer patients and 4 332 controls were included. The results of meta-analysis showed that significant association was found between TLR2 gene I/D polymorphism and the risk of cancer (DD+DI vs. Ⅱ:OR=1.60, 95%CI 1.13 to 2.27, P=0.009; DD vs. Ⅱ+DI:OR=1.73, 95%CI 1.13 to 2.66, P=0.01; DD vs. Ⅱ:OR=1.99, 95%CI 1.22 to 3.24, P=0.006; DI vs. Ⅱ:OR=1.52, 95%CI 1.09 to 2.11, P=0.01; D vs. I:OR=1.54, 95%CI 1.14 to 2.09, P=0.005). ConclusionTLR2 gene L/D polymorphism may be associated with cancer risk. Due to the limited quantity and quality of included studies, the conclusion should be verified in further studies.
ObjectiveTo investigate the effect and mechanism of ulinastatin to ventilator induced lung injury (VILI). MethodsTotal 24 SD rats were randomly divided into a control group, a VILI group, and a VILI+ ulinastatin group. High mobility group box-1 (HMGB-1), tumor necrosis factor (TNF)-α and interleukin (IL)-6 in bronchoalveolar lavage fluid, toll like receptor-4, dry/wet ratio and pathological scores of lung tissue were detected in the three groups. ResultsHMGB-1, TNF-α, and IL-6 in bronchoalveolar lavage fluid, toll like receptor-4, dry/wet ratio and pathological scores of lung tissue were significantly higher in the VILI group than those in the control group with statistical differences (P<0.05). While HMGB-1, TNF-α, and IL-6 in bronchoalveolar lavage fluid, toll like receptor-4, dry/wet ratio and pathological scores of lung tissue were reduced in the VILI+ ulinastatin group compared with those in the VILI group. ConclusionUlinastatin may protect ventilator induced lung injury by reducing inflammation level in lung through HMGB-1-TLR4 pathway.
ObjectiveTo observe the protective effect of tanshinone Ⅱ A on the mouse liver ischemia-reperfusion injury (IRI) model and preliminarily explore its mechanism of alleviating liver injury.MethodsThe IRI mouse model was established after the pre-treating with tanshinone Ⅱ A. Then, the serum and liver tissue of mice were collected to detect the changes of liver function, histopathology, liver cell apoptosis, and inflammatory factors. In addition, the protein expression levels of high mobility group box 1 (HMGB1), advanced glycosylation end-product specific receptor (RAGE), and Toll like receptor 4 (TLR4) in the liver tissues were detected by the Western blot method.ResultsAll data were analyzed by the homogeneity of variance test. The results of factorial design showed that the levels of ALT and AST in the serum, the pathological score and apoptosis index, the inflammatory response, as well as the expressions of HMGB1, TLR4 and RAGE proteins in the liver tissues were decreased significantly (P<0.05) in the sham operatation plus tanshinone Ⅱ A mice, which were increased significantly (P<0.05) in the IRI mice, which were antagonized synergistically by the tanshinone ⅡA and IRI (P<0.05).ConclusionsTanshinone ⅡA could reduce the liver IRI and inflammatory response in mouse. These effects might be related to the down-regulations of TLR4, HMGB1, and RAGE expressions.