聚己内酯/丝胶蛋白静电混纺膜炎症响应的体内评价

背景：研究表明,丝胶蛋白可以增加哺乳动物细胞的增殖,促进伤口愈合,具有良好的抗菌、抗氧化、抗癌的活性,同时具有良好的生物相容性和可降解性,是一种理想的组织工程材料。然而目前对丝胶蛋白能否引起炎症响应仍存在争论。 目的：评价聚己内酯/丝胶蛋白静电混纺膜的炎症响应。 方法：将不同混合比例的聚己内酯/丝胶蛋白纳米纤维薄膜体内埋植入大鼠背部肌肉,4周后取出进行组织学观察,通过苏木精-伊红染色和巨噬细胞抗体CD68免疫组织化学染色评价其炎症响应。 结果与结论：聚己内酯/丝胶蛋白7∶3组混纺膜炎症反应与丝素蛋白膜类似,小于聚己内酯/丝胶蛋白6∶4组、聚己内酯/丝胶蛋白5∶5组和聚己内酯组;聚己内酯/丝胶蛋白6∶4组与聚己内酯/丝胶蛋白5∶5组与聚己内酯组类似。提示聚己内酯/丝胶蛋白静电混纺膜不会引起显著的炎症响应,少量添加丝胶蛋白可以降低聚己内酯的炎症反应,随着丝胶蛋白含量的增加,炎症反应呈上升趋势。     

亚硒酸钠及维生素E调控小鼠肝血管炎症反应机制的研究

目的 验证亚硒酸钠及维生素Ｅ对补体活化与中性粒细胞产生活性氧之间相互反馈活化、增强炎症反应的机制具有调节作用。方法 以补体活化抑制剂、亚硝酸钠及抗氧化自由基清除剂维生素Ｅ阻断补体－活性氧之间的活化反馈作用,在试管及小鼠肝血管炎模型体内,分别利用化学发光检测氧自由基的发生量及免疫学方法检测补体的活化程度和血管炎的发生。结果 亚硝酸钠及维生素Ｅ可抑制“活化反馈”环的上调炎症反应作用,而抑制了小鼠实验肝     

Strain dependence in murine models of monoarthritis

Objective and design: This study explores the inflammatory response in various murine strains. Utilising several approaches, monoarthritis was induced in the knee, providing an inflammatory model relevant to arthritis. Methods: Acute (carrageenan/kaolin; C/K) or chronic inflammatory models (Freund’s complete adjuvant; FCA) or antigen-induced arthritis (AIA), were induced by peri- and/or intra-articular injection. Results: C/K elicited an acute inflammatory response in various strains of mice, with significant (P < 0.005) phenotypic variation. FCA induction provided a chronic inflammatory response. The magnitude of the response in both acute and chronic models was strain dependent, with BalbC exhibiting the most resistance to swelling in all models. AIA produced only an acute response in three strains tested. Conclusions: The data presented, demonstrating variation in the magnitude of acute and chronic inflammatory responses in different mice strains, allows informed selection of appropriate strains and models for future experimental studies. Received 28 March 2007; returned for revision 1 June 2007; accepted by J. Di Battista 27 June 2007     

Bone marrow cell response following induction of acute inflammation in different strains of mice

The magnitude of the macrophage inflammatory response differs among inbred mouse strains. Mice of the A/J strain respond poorly to sterile inflammatory stimuli while those of the C57BL/6 strain show a strong response. Inflammatory macrophages found at the site of inflammation are the product of bone marrow (BM) myeloid stem cells. Mice of the A/J strain were found to have half the number of BM nucleated cells per femur than those of the C57BL/6 strain. The lower BM cellularity may be one reason for the poor macrophage inflammatory response observed in A/J mouse strain. Using A×B/B×A recombinant inbred mouse strains, we determined that the number of nucleated cells per femur found in normal mice was not a determining factor of the magnitude of the macrophage inflammatory response. One additional explanation for the poor macrophage inflammatory response in mice of the A/J strain is their deficiency in the C5 component of complement. Using a C5-sufficient A/J.C5 congenic strain, we have previously shown that the presence of C5 on the A/J background improved their inflammatory response. We compared A/J and A/J.C5 mouse strains to determine whether or not C5 had an impact on the BM cell response to inflammatory stimulus. The presence of C5 on the A/J background could contribute to the improvement of the inflammatory response in mice of the A/J.C5 strain by inducing a greater number of nucleated cells to exit the BM compartment early following induction of inflammation.     

The chemokine receptor D6 limits the inflammatory response in vivo

How the inflammatory response is initiated has been well defined but relatively little is known about how such responses are resolved. Here we show that the D6 chemokine receptor is involved in the post-inflammatory clearance of beta-chemokines from cutaneous sites. After induction of inflammation by phorbol esters, wild-type mice showed a transient inflammatory response. However, in D6-deficient mice, an excess concentration of residual chemokines caused a notable inflammatory pathology with similarities to human psoriasis. These results suggest that D6 is involved in the resolution of the cutaneous inflammatory response.     

Role of adrenomedullin in Lyme disease

Borrelia burgdorferi stimulates a strong inflammatory response during infection of a mammalian host. To understand the mechanisms of immune regulation employed by the host to control this inflammatory response, we focused our studies on adrenomedullin, a peptide produced in response to bacterial stimuli that exhibits antimicrobial activity and regulates inflammatory responses by modulating the expression of inflammatory cytokines. Specifically, we investigated the effect of B. burgdorferi on the expression of adrenomedullin as well as the ability of adrenomedullin to dampen host inflammatory responses to the spirochete. The concentration of adrenomedullin in the synovial fluid of untreated Lyme arthritis patients was elevated compared with that in control osteoarthritis patient samples. In addition, coculture with B. burgdorferi significantly increased the expression of adrenomedullin in RAW264.7 macrophages through MyD88-, phosphatidylinositol 3-kinase (PI3-K)-, and p38-dependent signaling cascades. Furthermore, the addition of exogenous adrenomedullin to B. burgdorferi-stimulated RAW264.7 macrophages resulted in a significant decrease in the induction of proinflammatory cytokines. Taken together, these results suggest that B. burgdorferi increases the production of adrenomedullin, which in turn negatively regulates the B. burgdorferi-stimulated inflammatory response.     

Acute Immune and Non-Immune Inflammatory Response in Spontaneously Hypertensive Rats and Normotensive Rats. Role of Endogenous Nitric Oxide

Summary The present study investigated the acute inflammatory response (increase in vascular permeability and leukocytes migration) in the pleura of spontaneously hypertensive rats (SHR) and normotensive rats (NTR), using two different stimulus: carrageenan and active anaphylaxis. In addition, the role of endogenous nitric oxide in these responses was investigated. Results The inflammatory response induced by intrapleural carrageenan injection in SHR developed similarly to that in NTR. Treatment with L-NAME, reduced the intensity of this response in both groups of rats. The inflammatory response induced by active anaphylaxis in SHR and NTR was different. The increase in vascular permeability occurred later in the SHR compared to NTR. The number of leukocyte present in inflammatory exudates was increased at 4 h in both groups of rats. L-NAME treatment did not inhibit exudation at the intervals under analysis, however, reduced the number of mononuclear cells in the inflammatory exudate of SHR. Conclusion The development of the inflammatory response in SHR differs from that in NTR, depending on the nature of the inflammatory stimulus. Endogenous NO plays a clear role in carrageenan-induced inflamma-tion, but not in immunologically mediated inflammation in the analyzed period.     

Relationship between perioperative inflammatory response and postoperative cognitive dysfunction in the elderly

After surgery and anesthesia, many elderly patients show a decline in cognitive function. This condition is called postoperative cognitive dysfunction (POCD). POCD, a distressing complication after surgery, is independently associated with poor short-term and long-term outcomes. Many pathophysiological mechanisms have been implicated in development of POCD, but the exact cascade leading to its development is unclear. Animal studies show that cytokines from inflammatory response are involved in with cognitive dysfunction. Simultaneously, emerging evidences indicate that inflammatory response represents a potential pathogenic factor in many central cognitive diseases. A similar story may be occurring during perioperative process in patients. Surgical trauma, anesthesia, and stress response induced perioperative nonspecific inflammatory response. We hypothesize that perioperative inflammatory response promotes the development of POCD in elderly surgical patients, and some measures against perioperative inflammatory response should be considered as a new pathway to prevention of POCD.     

Research progress of B subfamily of leucocyte immunoglobulin-like receptors in inflammation

Leucocyte immunoglobulin-like receptors subfamily B (LILRB) belongs to the type I transmembrane glycoproteins, which is the immunosuppressive receptor. LILRBs are widely expressed in bone marrow cells, hematopoietic stem cells, nerve cells and other body cells. Studies have found that LILRBs receptor can bind to a variety of ligands and has a variety of biological functions such as regulating inflammatory response, immune tolerance and cell differentiation. Inflammatory reaction plays a vital role in resisting microorganisms. The function of inhibitory immune receptors can recognize the signs of infection and promote the function of anti-microbial effect. The inflammatory response must be strictly regulated to prevent excessive inflammation and tissue damage. Therefore, it is of general interest to understand the role of LILRBs in the inflammatory response. Because they can inhibit the anti-microbial response of neutrophils, some human pathogens use these receptors to escape immunity. This article reviews the biological role of LILRBs in the inflammatory response. We focus on the known ligands of LILRBs, their different roles after binding with ligands, and how these receptors help to form neutrophil responses during infection. Recent studies have shown that LILRBs recruit phosphatases through intracellular tyrosine-based immunoreceptor inhibitory motifs to negatively regulate immune activation, thereby transmitting inflammation-related signals, suggesting that LILRBs may be an ideal target for the treatment of inflammatory diseases. Here, we describe in detail the regulation of LILRBs on the inflammatory response, its signal transduction mode in inflammation, and the progress in the treatment of inflammatory diseases, providing a reference for further research.     

Systemic inflammatory response syndrome: new concepts

Systemic inflammatory response syndrome is secondary to several insults whose purpose is to limit and reverse the injury. The outcome and intensity of the inflammatory response is determined by injury extension and balance between inflammatory and compensatory antiinflammatory responses. The interaction of the several soluble and cellular mediators of inflammatory and antiinflammatory responses determine the next evolutive phases: a) local inflammatory response; b) systemic inflammatory response; c) massive systemic inflammatory response; d) immunologic paralysis; and e) immune dissonance. If the last three phases do not control, cell damage can be amplified and thus perpetuating the infectious process and leading the patient to multiple organ dysfunction. Gamma interferon and steroids as modulators of the inflammatory response, in stages of paralysis and immune dissonance has been studied in clinical and experimental trials with promising results, but more studies to are needed validate their usefulness.     

微小RNA在力相关牙周炎症反应和组织改建中的作用

微小核糖核酸(micro-ribonucleic acid,miRNA)是一种非编码单链RNA分子,可通过抑制靶基因mRNA的翻译来调控生物体遗传信息表达,参与体内多种生物学过程的发生发展.miRNA在机械力诱导机体产生的炎症性疾病和组织改建中发挥着重要作用.牙周组织中机械力敏感细胞可在力作用下导致牙周组织炎症反应、组...     

Anaphylatoxins in organ transplantation

C3a and C5a (also called anaphylatoxins) are inflammatory peptides generated during complement activation. They do not only play important roles in innate immunity through the initiation and regulation of inflammatory responses, but also significantly influence adaptive immune responses. Organ transplantation triggers an initial inflammatory response and subsequent to the specific immune response (also called the alloimmune response), both of which contribute to graft rejection. Emerging evidence suggests that anaphylatoxins, particularly C5a, are significantly involved in both inflammatory and alloimmune responses following organ transplantation, thus influencing graft outcome. This review will provide the information on our current understanding of the roles for anaphylatoxins in ischemia–reperfusion injury, graft rejection, and transplant tolerance, and the therapeutic potential of targeting anaphylatoxin receptors in organ transplantation.     

In vitro and in vivo activation of polymorphonuclear leukocytes in response to particulate debris

The host inflammatory response to particulate wear debris has been implicated as a principal cause of osteolysis and aseptic loosening following total joint arthroplasty. While it has long been assumed that this inflammatory response is mediated solely by a chronic process, there has been evidence to suggest that an acute response to particulate debris may be important in initiating the chronic response. We studied the in vitro and in vivo acute inflammatory responses mediated by polymorphonuclear leukocytes (PMNs) to both retrieved particulate from a catastrophically failed uncemented metal-backed acetabular component and to commercially pure particulate (polyethylene, cobalt-chrome, and titanium). Isolated, nonactivated human PMNs in vitro exhibited both a dose- and time-dependent degranulation response to opsonized particulate debris, as evidenced by release of both specific (increased lysozyme activity) and azurophilic (increased beta-glucuronidase activity) granule contents. In the rat subcutaneous pouch model in vivo, PMNs were recruited within 3-6 h after exposure to particulate debris and were noted to phagocytize particulate and subsequently degranulate, as evidenced by increased beta-glucuronidase and PMN-specific myeloperoxidase (azurophilic granule enzymes) activities. This response peaked within the first 6 h and gradually declined by 24 h. The results of this study demonstrate the presence of an acute inflammatory response mediated by PMNs both in vitro and in vivo to particulate debris, which may be important in the sequence of events that lead to the macrophage-dominated chronic inflammatory process culminating in osteolysis and aseptic loosening of total joint arthroplasties.     

Saturated fatty acids activate the inflammatory signalling pathway in Schwann cells: Implication in sciatic nerve injury

Sciatic nerve injury affects quality of life. Many immune cells and inflammatory cytokines have been reported to be involved in sciatic nerve injury, but little is known about the ligands and receptors that trigger inflammatory responses. By using a modified sciatic nerve clamp injury method, we found that the recruitment of Schwann cells and the inflammatory response were enhanced after sciatic nerve injury. Toll-like receptor 4 (TLR4), one of the major members of the TLR family, is highly expressed in Schwann cells. Under certain conditions, myeloid differentiation protein 2 (MD2) binds to TLR4 on the membrane and plays important roles in the inflammatory response. The reductions in the recruitment of Schwann cells and the inflammatory response induced by the blockade of TLR4 or MD2 suggest that TLR4 and MD2 are involved in sciatic nerve injury. What are the endogenous signals that activate the inflammatory response? A large number of free saturated fatty acids (SFAs) are released from Schwann cells, adipocytes and the blood after sciatic nerve injury. Liang et al reported that Schwann cells can be stimulated by palmitic acid (PA). Here, we found that the expression and secretion of TNF-α and IL-6 were enhanced by PA treatment. Moreover, PA activated TLR4 signalling pathway-related proteins and stimulated a strong association between TLR4 and MD2. Blocking TLR4 or MD2 reversed the PA-induced inflammatory response and TLR4 downstream signalling pathway. Thus, we speculated that SFAs act as endogenous ligands that activate TLR4/MD2, thus triggering Schwann cell inflammation during sciatic nerve injury.     

Mediators of substance P-induced inflammation in the rat knee joint

Substance P (SP) injected into the synovial cavity of the rat knee resulted in an inflammatory response as measured by plasma protein extravasation into the joint capsule. This response was dose dependant over the range of 4 M to 200 M. Part of this inflammatory response was mediated via mast cells as pre-treatment of the animals with a mast cell degranulator (compound 48/80) resulted in a 66% reduction of the response. A direct effect of SP on the vascular receptors may also contribute to the inflammatory response as pre-treatment with the substance P antagonist (SPA)d-Pro ⁴ d-Trp ^7,9,10 SP_4–11 also reduces the inflammatory response. Intra-articular injections of the H₁ blocker diphenhydramine or the H₂ blocker cimetidine significantly blocked the SP-induced inflammatory response. The 5-hydroxytryptamine (5-HT) antagonist methysergide proved to be even more potent in blocking the SP-induced inflammatory response. No synergistic inhibition was observed with combinations of the different antagonists. Intra-articular injections of 5-HT elicited a much more pronounced inflammatory response than that produced by a 10-fold higher concentration of histamine.The results suggest that SP produces increased vascular permeability partly via direct actions on the blood vessels and partly via mast cells. The inflammatory response occuring via mast cells appears to be mediated by histamine and to a greater extent by 5-HT.     

Role of chemokines in the pathogenesis of acute lung injury

Acute lung injury (ALI) is due to an uncontrolled systemic inflammatory response resulting from direct injury to the lung or indirect injury in the setting of a systemic process. Such insults lead to the systemic inflammatory response syndrome (SIRS), which includes activation of leukocytes-alveolar macrophages and sequestered neutrophils-in the lung. Although systemic inflammatory response syndrome is a physiologic response to an insult, systemic leukocyte activation, if excessive, can lead to end organ injury, such as ALI. Excessive recruitment of leukocytes is critical to the pathogenesis of ALI, and the magnitude and duration of the inflammatory process may ultimately determine the outcome in patients with ALI. Leukocyte recruitment is a well orchestrated process that depends on the function of chemokines and their receptors. Understanding the mechanisms that contribute to leukocyte recruitment in ALI may ultimately lead to the development of effective therapeutic strategies.     

抗菌肽在炎症治疗方面的进展

抗菌肽参与免疫反应的多个步骤,可调节炎性反应,成为了极具潜力的临床治疗方法。本文将阐述抗菌肽在炎症相关疾病治疗中的作用及应用。     

Differences in the early inflammatory responses to toxin-induced demyelination are associated with the age-related decline in CNS remyelination

CNS remyelination occurs more rapidly in young adult rats than in old rats. Since the inflammatory response initiated by demyelination is an important trigger for remyelination, we address whether ageing changes in remyelination are associated with changes in the inflammatory response. Using a toxin model of demyelination, where the inflammatory response largely comprises macrophages, we show that there is a delay in both recruitment and activation of OX-42+ and macrophage scavenger receptor B+ macrophages following demyelination in older rats (10-13 months) compared to young rats (8-10 weeks). This difference is associated with a slower onset of increased expression of several chemokine mRNAs. However, many inflammatory cytokines have similar mRNA expression patterns, with the exception of IL-1beta, IL-6 and TNF-alpha, which have prolonged expression in the older animals. Differences in IL-1beta mRNA expression, a cytokine specifically implicated in CNS remyelination, are not reflected in differences in protein expression detected by immunocytochemistry. These data relate the age-associated delay in remyelination efficiency to changes in the macrophage and inflammatory mediator response to demyelination.     

冠状动脉支架置入后相关炎症因子的变化及其干预

背景：冠状动脉粥样硬化性心脏病支架置入治疗后的炎症反应以及其严重程度与再狭窄明显存在相关性,医学工作者试图从中寻找新思路预防支架置入后再狭窄,提高治疗质量。 目的：评价各种干预措施以及监测手段在冠状动脉置入术后炎症治疗中的应用价值和临床前景。 方法：电子检索EMbase(1980-01/2011-05),MEDLINE(1966-01/2011-05),中国生物医学文献数据库(CBM,1978/2011-05)和中国期刊全文数据库(CNKI),筛查相关文章的参考文献。中文检索词“冠状动脉支架,炎症因子,炎症,CRP,再狭窄”,英文检索词为“Coronary stent,inflammatory cytokines,inflammation,CRP,restenosis”。 结果与结论：临床试验结果显示支架置入后炎症反应明显加重,使用雷帕霉素药物洗脱支架,添加地塞米松、塞来昔布、瑞舒伐他汀等可更大程度上降低支架置入后炎症反应。动物试验发现使用雷帕霉素洗脱支架可减少支架置入段新生内膜的形成和缩小炎症面积。提示各种干预措施可降低支架置入后炎症反应从而降低远期再狭窄的发生,可进一步改良加以应用于临床观察其疗效。