Current therapies for autoimmune diseases are not cures but merely palliatives, aimed at reducing symptoms. For the most part, these treatments provide nonspecific suppression of the immune system and thus do not distinguish between a pathogenic autoimmune response and a protective immune response. Recently emerging evidence not only has indicated the involvement of members of the TNF receptor/ligand superfamilies but also has revealed exciting innovative strategies for the treatment of autoimmune diseases and other chronic inflammatory diseases without depressing the immune response in general. In this review, we will discuss the regulatory mechanisms of TNF receptor/ligand family members, such as HVEM/ LIGHT, 4-1BB/4-1BBL, and GITR/GITRL that regulate T and B cell functions and participate in the process of inflammatory diseases. We will also discuss how intervening in the costimulatory pathways mediated by these molecules might have some potential as a therapeutic approach to immune disorders.
Animals ; Apoptosis ; Autoimmune Diseases/immunology/metabolism/pathology ; B-Lymphocytes/immunology/physiology ; Dendritic Cells/physiology ; Human ; Inflammation/*immunology ; Lymphocyte Activation/immunology ; Models, Biological ; Receptors, Tumor Necrosis Factor/*physiology ; T-Lymphocytes/immunology/physiology ; Tumor Necrosis Factor/immunology/*physiology

OBJECTIVETo review the relationship between the immune system and the mechanism of pain. Data sources Related researches published in the period of 1987-2005 were systematically reviewed. Study selection Articles about the immune system and pain were selected. Data extraction Data were mainly extracted from 74 articles which are listed in the reference section of this review.

RESULTSPain was classically viewed as being mediated solely by neurons. However, growing evidence has showed the possible relationships between the immune system and the central nervous system. In this article, we reviewed the role of the immune system in the development of pain, together with the importance of the glia in this process. These findings suggest a novel approach to pain control in the future.

CONCLUSIONSThe immune system plays a potential but important role in the development of pain.

Animals ; Brain ; immunology ; Humans ; Immune System ; physiology ; Interleukin-1 ; physiology ; Neuroglia ; physiology ; Pain ; etiology ; immunology ; TRPV Cation Channels ; physiology ; Tumor Necrosis Factor-alpha ; physiology ; Wounds and Injuries ; immunology

Periodontitis is an inflammatory disease involving the destruction of both soft and hard tissue in the periodontal region. Although dysbiosis of the local microbial community initiates local inflammation, over-activation of the host immune response directly activates osteoclastic activity and alveolar bone loss. Many studies have reported on the cytokine network involved in periodontitis and its crucial and pleiotropic effect on the recruitment of specific immunocytes, control of pathobionts and induction or suppression of osteoclastic activity. Nonetheless, particularities in the stimulation of pathogens in the oral cavity that lead to the specific and complex periodontal cytokine network are far from clarified. Thus, in this review, we begin with an up-to-date aetiological hypothesis of periodontal disease and summarize the roles of cytokines in the host immune response. In addition, we also summarize the latest cytokine-related therapeutic measures for periodontal disease.
Alveolar Bone Loss ; etiology ; Cytokines ; metabolism ; physiology ; Humans ; Inflammation ; Periodontal Diseases ; Periodontitis ; immunology ; microbiology ; Tumor Necrosis Factor-alpha ; physiology

BACKGROUNDRev is necessary for exporting unspliced and incompletely spliced intron containing HIV mRNAs and for HIV replication. The aim of this study is to develop a kind of selective suicide construct that can specifically and directly induce HIV infected cells into apoptosis based on the high affinity of Rev and Rev response element (RRE).

METHODSMolecular-cloning technique was used to synthesis Rev dependent TNF-R1 expression construct pDM128-TNF-R1 (pT128) that contains RRE and TNFR1 gene. Restriction digestion, Polymerase Chain Reaction (PCR) and DNA sequencing were processed and the exactness and correctness of the inserted TNF-R1 gene in pT128 were confirmed repeatedly. The expression of pT128 co-transfected with different combination of other plasmids by calcium phosphate-DNA co-precipitation in Helas and by gene gun transfection in keratinocytes was further tested by flow-cytometry and cell counted under microscope.

RESULTSThe new plasmid specifically expressed TNF-R1 in Helas when co-transfected with pRev but did not when without pRev. Indirect expression of TNF-R1 from pT128 was slower than the direct expression of that from Hu p60 TNFR1 in pDC302 (pT60), but all those pT60 or pT128 transfected cells showed apoptosis at last while TNF-R1 was sufficiently expressed. Other kinds of Rev expression construct such as pAD8 and a chimeric HIV vaccine also can switched on the selective expression of pT128. Not only Rev-dependent expression in Helas, pT128 also normally expressed its TNF-R1 in keratinocytes. Co-transfected with pRev or pAD8 that expressed Rev, pT128 expressed TNF-R1 and induced apoptosis of green fluorescent keratinocytes in skin explant. The number of green fluorescent keratinocytes co-transfected by pT128 plus pRev or pAD8 was gradually outnumbered by that co-transfected by pT128 only. The difference was more significant after culturing for 72 hours.

CONCLUSIONSRev dependent pT128 is able to selectively induce apoptosis of HIV-infected or Rev-expressed target cells by expression of TNF-R1. The new strategy based on manipulation of the regulatory protein of HIV may be valuable in design of new HIV vaccine.

AIDS Vaccines ; immunology ; Apoptosis ; Biolistics ; Cell Line, Tumor ; Gene Products, rev ; physiology ; Genes, env ; physiology ; Genetic Vectors ; Humans ; Keratinocytes ; metabolism ; Plasmids ; Receptors, Tumor Necrosis Factor, Type I ; genetics

Cytokines ; physiology ; Humans ; Interferon-gamma ; physiology ; Interleukin-1 ; physiology ; Interleukin-10 ; physiology ; Interleukin-12 ; physiology ; Interleukin-6 ; physiology ; Interleukin-8 ; physiology ; Rotavirus Infections ; immunology ; Tumor Necrosis Factor-alpha ; physiology

OBJECTIVETo investigate the curative effect and histocompatibility of reconstruction of traumatic urethral defect of rabbit using urethral extracellular matrix (ECM).

METHODSUrethral ECM was obtained by excision of the urethra in 20 donor rabbits. In experimental group, 20 rabbits were resected a 1.0 cm-1.5 cm segment of the urethra and artificially made a model of traumatic urethral defect, then reconstructed by the urethral extracellular matrix of the same length. The rabbit immunity response was assessed by lymphocyte transformation test and serum TNF-alpha level. The reconstructed urethral segments were stained with hematoxylin-eosin and Van Gieson stain and observed by histological examination postoperatively. The urethrography, urethroscopy and urodynamic examinations were performed.

RESULTSThere was no significant difference in stimulative index of lymphocyte transformation between ECM group and control group. The serum TNF-alpha levels of ECM group slightly rose, but the increase was not significant as compared with control group. On postoperative day 10, epithelial cell had migrated from each side and small vessels were found in the extracellular matrix. In the 3rd week, several layers of urothelium covered the whole surface of the matrix tube. In the 6th week, the disorganized arrangements of smooth muscle fibers were firstly observed by Van Gieson staining. In the 24th week, the smooth muscle cells increased and the matrix tube appeared fairly similar to normal urethral wall components. The urethroscopy and urodynamic evaluation revealed that the surface of reconstructed urethra was smooth and emiction was unobstructed.

CONCLUSIONThe urethral extracellular matrix might be an ideal and safe biomaterial for the reconstruction of urethral traumatic defect.

Animals ; Extracellular Matrix ; immunology ; physiology ; Female ; Immunohistochemistry ; Lymphocyte Activation ; Rabbits ; Reconstructive Surgical Procedures ; methods ; Tumor Necrosis Factor-alpha ; blood ; Urethra ; immunology ; injuries ; surgery

The brain modulates the immune system in an asymmetrical way, as shown by the association between paw preference and immune response in the mice. The purpose of the present work was to study the relationship between plasma tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO) and nitric oxide synthase (NOS) and brain lateralization. In the study, paw preference test was used to select right-pawed, left-pawed and ambidextrous mice. Mice were classified as the right-pawed if the right paw entry (RPE) score was equal to or greater than 30 (30-50), as the left-pawed if the score was equal to or less than 20 (0-20), and as the ambidextrous if the score was between 21 and 29. One week after the paw preference testing, the animals were injected intraperitoneally with either sterilized 0.9% saline or lipopolysaccharide (LPS) (5 microg/0.5 ml NS) and were killed 2 h later. Plasma was collected from each mouse. The level of plasma TNF-alpha was measured with ELISA kits provided by ENDOGEN. NO and NOS levels of plasma were detected with kits from Juli Biotechnology Company. The results showed that (1) in the normal mice, ambidextrous mice had higher NO levels compared with left-pawed mice (P<0.05). After the injection of LPS, plasma level of TNF-alpha was lower in left-pawed mice compared with those of the right-pawed and ambidextrous mice; plasma level of NO was higher in ambidextrous mice compared with those of the right- (P<0.01) and left-pawed (P<0.05) ones, and there was no significant difference in the plasma levels of NOS among ambidextrous, right- and left-pawed mice. (2) Immune parameters were correlated with the RPE scores. The shape of the curve describing this relation was similar to a parabola. In general, the levels of TNF-alpha, NO, NOS rose along with the increase of RPE if the scores were in the score range of left-pawed mice.After that, they reached a peak if the scores were in the score range of ambidextrous mice. Then they declined along with the increase of RPE if the scores were in the score range of right-pawed mice. In conclusion, plasma levels of TNF-alpha, NO and NOS were associated with brain lateralization, suggesting that the activities of Mo/Mphi were influenced by brain lateralization, and that the immune parameters were correlated with the RPE scores.
Animals ; Brain ; physiology ; Female ; Functional Laterality ; physiology ; Macrophages ; immunology ; Mice ; Mice, Inbred BALB C ; Nitric Oxide ; blood ; Nitric Oxide Synthase ; blood ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo understand the effects of the IL-1, TNF-alpha cytokines on the pathogenesis of periapical lesions by investigating its gene expression in rat.

METHODSThe model was established by surgically exposing mandibular molar teeth and left open to permit infection from the oral environment. The SD rats were killed at 1, 2, 3, 4 weeks and mandibular molar teeth X-ray were taken. In situ hybridization was used to test IL-1alpha, IL-1beta, TNF-alpha mRNA expression in periapical area and the kinds of positive cells were identified. Using image analysis system analyzed gene expression semi-quantified.

RESULTSIL-1alpha, IL-1beta and TNF-alpha mRNA were all expressed beginning at 1 week, peaked at 3 weeks, and declined somewhat at 4 weeks, but IL-1beta mRNA was expressed at much lower levels with the same kinetics (P<0.01). Most of the staining occurred in areas that had heavy inflammatory infiltrate, fibroblasts, or endothelial cells. There was a statistically significant correlations between the area of periapical lesion and the number of positively stained cells for IL-1alpha and for TNF-alpha (IL-1alpha: r=0.875, P<0.001; TNF-alpha: r=0.858, P<0.001), and between the number of positive cells for IL-1alpha and that of for TNF-alpha (r=0.969, P<0.001).

CONCLUSIONSIL-1alpha and TNF-alpha genes are highly expressed in developing periapical lesions in rat, which supports the hypothesis that these two cytokines play a key role in pulpal and periapical pathogenesis, including the concomitant bone destruction.

Animals ; In Situ Hybridization ; Interleukin-1 ; genetics ; physiology ; Periapical Periodontitis ; etiology ; immunology ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; genetics ; physiology

OBJECTIVETo explore the immune mechanism of moxibustion on protecting gastric mucosa injury.

METHODSForty healthy SD rats were randomly divided into four groups: a blank group, a model group, a moxibustion acupoint group and a moxibustion non-acupoint group, 10 rats in each one. Eight days before model establishment, moxibustion at "Zusanli" (ST 36), "Zhongwan" (CV 12), "Guanyuan" (CV 4), "Pishu" (BL 20) and "Weishu" (BL 21) was applied in the moxibustion acupoint group while these acupoints' controlled points were selected in the moxibustion non-acupoint group, and no treatment was given in the model group, once a day in three groups for continuous 16 days. The helicobacter pylori (Hp) model was established by intragastric administration of Hp. HE staining microscopic examination was used to observe inflammation severity in gastric mucosa, and enzyme-linked immunosorbent assay (ELISA) was adapted to measure content of heat shock protein (HSP) 72, TNF-alpha and IL-1beta, and real-time quantitative PCR was used to measure the expression of TLR2 mRNA, TLR4 mRNA, CD14 mRNA and MyD88 mRNA in peripheral blood mononuclear cells, and western blot method was used to measure content of NFkappaB and IkappaBalpha in peripheral blood mononuclear cells.

RESULTSCompared with the blank group, the expression of HP could be seen in the smear of gastric mucosa by Gram's staining in the model group; the inflammation severity score was obviously increased as well as content of serum HSP 72 and TNF-alpha and IL-1beta in gastric tissue; and expression of TLR2, 4 mRNA, CD14 mRNA, MyD88 mRNA, NFkappaB was increased (P < 0.01), but the expression of IkappaBalpha was reduced (P < 0.05). After the moxibustion, the inflammation severity score was reduced in the moxibustion acupoint group, and the content of serum HSP 72 was increased, and the expression of TNF-alpha and IL-1beta in gastric tissue and expression of TLR2 mRNA, TLR4 mRNA, CD14 mRNA, MyD88 mRNA and NFkappaB were reduced (P < 0.01), but the expression of IkappaBalpha was increased (P < 0.05). The differences between the moxibustion non-acupoint group and the model group were not significant (P > 0.05).

CONCLUSIONThe pretreatment of moxibustion at acupoints could induce the over expression of serum HSP 72. By combining TLR 2 and 4 receptors to trigger receptor signal transduction pathways, the releases of downstream signal substances are regulated; as a result, the releases of related immune substances are regulated to relieve the gastric mucosa injury of rats with HP gastritis.

Acupuncture Points ; Animals ; Female ; Gastritis ; immunology ; therapy ; Helicobacter Infections ; genetics ; immunology ; therapy ; Helicobacter pylori ; physiology ; Humans ; Interleukin-1beta ; genetics ; immunology ; Male ; Moxibustion ; NF-kappa B ; genetics ; immunology ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; genetics ; immunology

Idiopathic thrombocytopenia purpura (ITP) is an autoimmune disease which is characterized by destruction of platelets by macrophages in the reticuloendothelial system. Recent studies suggest that ITP is related to the abnormal activation and apoptosis of T/B cells which lead to failure of immune tolerance. Now it is becoming clear that costimulatory signals are required for full T/B cell activation and assumed to modulate T/B cells responses as well as other aspects of the immune system. This review focuses on the role and state-of-the-art advancements of costimulatory signals in ITP.
Antigens, CD ; immunology ; Antigens, Differentiation ; immunology ; Antigens, Differentiation, T-Lymphocyte ; immunology ; B-Lymphocytes ; immunology ; CD28 Antigens ; immunology ; CTLA-4 Antigen ; Humans ; Immune Tolerance ; Inducible T-Cell Co-Stimulator Protein ; Purpura, Thrombocytopenic, Idiopathic ; immunology ; Receptors, Tumor Necrosis Factor ; immunology ; Signal Transduction ; physiology ; T-Lymphocytes ; immunology ; physiology