The Notch signaling pathway is conserved from Drosophila to mammals and is critically involved in developmental processes. In the immune system, it has been established that Notch signaling regulates multiple steps of T and B cell development in both central and peripheral lymphoid organs. Relative to the well documented role of Notch signaling in lymphocyte development, less is known about its role in regulating myeloid lineage development and function, especially in the context of acute and chronic inflammation. In this review article, we will describe the evidence accumulated during the recent years to support a key regulatory role of the Notch pathway in innate immune and inflammatory responses and discuss the potential implications of such regulation for pathogenesis and therapy of inflammatory disorders.
Animals ; B-Lymphocytes ; immunology ; pathology ; Humans ; Inflammation ; immunology ; pathology ; Receptors, Notch ; immunology ; Signal Transduction ; immunology ; T-Lymphocytes ; immunology ; pathology

The testis is an immune privileged organ where germ cells are protected from autoimmune attack to ensure its reproductive function. Immune tolerance is important for the normal development and function of the testis. Notwithstanding its immune-privileged status, the imbalance between the tolerogenic and the efferent limb of the testicular immune response may lead to autoimmune damage in inflammatory or infected circumstances. Testicular immune regulation is a complex system involving multiple factors and the study of the regulation mechanisms of the testis is of great significance for access to new therapeutic targets. Currently, testicular immunoregulation is thought to be related with blood-testis barrier, Sertoli cells, immune cells, cytokines and androgen.
Humans ; Immune Tolerance ; Inflammation ; Male ; Testis ; immunology ; pathology

The rising number of obese individuals has become a major burden to the healthcare systems worldwide. Obesity includes not only the increase of adipose tissue mass but importantly also the altered cellular functions that collectively lead to a chronic state of adipose tissue inflammation, insulin resistance and impaired wound healing. Adipose tissue undergoing chronic inflammation shows altered cytokine expression and an accumulation of adipose tissue macrophages (ATM). The macrophage migration inhibitory factor (MIF) superfamily consists of MIF and the recently identified homolog D-dopachrome tautomerase (D-DT or MIF-2). MIF and D-DT, which both bind to the CD74/CD44 receptor complex, are differentially expressed in adipose tissue and have distinct roles in adipogenesis. MIF positively correlates with obesity as well as insulin resistance and contributes to adipose tissue inflammation by modulating ATM functions. D-DT, however, is negatively correlated with obesity and reverses glucose intolerance. In this review, their respective roles in adipose tissue homeostasis, adipose tissue inflammation, insulin resistance and impaired wound healing will be reviewed.
Adipose Tissue/*immunology/pathology ; Animals ; Diabetes Mellitus/immunology/pathology ; Humans ; Inflammation/*immunology/pathology ; Insulin Resistance ; Intramolecular Oxidoreductases/analysis/*immunology ; Macrophage Migration-Inhibitory Factors/analysis/*immunology ; Macrophages/immunology/pathology ; Obesity/*immunology/pathology ; *Wound Healing

The rising number of obese individuals has become a major burden to the healthcare systems worldwide. Obesity includes not only the increase of adipose tissue mass but importantly also the altered cellular functions that collectively lead to a chronic state of adipose tissue inflammation, insulin resistance and impaired wound healing. Adipose tissue undergoing chronic inflammation shows altered cytokine expression and an accumulation of adipose tissue macrophages (ATM). The macrophage migration inhibitory factor (MIF) superfamily consists of MIF and the recently identified homolog D-dopachrome tautomerase (D-DT or MIF-2). MIF and D-DT, which both bind to the CD74/CD44 receptor complex, are differentially expressed in adipose tissue and have distinct roles in adipogenesis. MIF positively correlates with obesity as well as insulin resistance and contributes to adipose tissue inflammation by modulating ATM functions. D-DT, however, is negatively correlated with obesity and reverses glucose intolerance. In this review, their respective roles in adipose tissue homeostasis, adipose tissue inflammation, insulin resistance and impaired wound healing will be reviewed.
Adipose Tissue/*immunology/pathology ; Animals ; Diabetes Mellitus/immunology/pathology ; Humans ; Inflammation/*immunology/pathology ; Insulin Resistance ; Intramolecular Oxidoreductases/analysis/*immunology ; Macrophage Migration-Inhibitory Factors/analysis/*immunology ; Macrophages/immunology/pathology ; Obesity/*immunology/pathology ; *Wound Healing

OBJECTIVETo investigate whether the level of hepatitis B surface antigen (HBsAg) represents the status of inflammation and stages of fibrosis in livers of patients with chronic hepatitis B (CHB) during the immune clearance phase (IC).

METHODSLiver biopsy samples and sera were collected from 165 consecutive patients (136 males; 29 females) with CHB in IC who were treated in our hospital between March 2009 and June 2011. Routine biochemical tests were carried out to measure indicators of liver function. The relation between HBsAg level and liver pathological stages were determined by Spearman's rank correlation analysis. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of HBsAg level for liver pathological stages. Binary logistic regression was used to analyze potentially relevant indicators, and liver pathology-predicting models were built and analyzed by the ROC method.

RESULTSThe mean values of HBsAg (IU/mL) were significantly different at the different liver inflammation stages: G1, 27 716.07+/-32 870.69; G2, 34 478.75+/-40 899.55; G3, 19 408.09+/-24 881.07; G4, 14 286.31+/-28 610.14. Likewise, the mean values of HBsAg (IU/mL) were significantly different at the different liver fibrosis stages: S1, 41 337.23+/-43 236.39; S2, 27 264.32+/-32 517.29; S3, 111 541.77+/-11 538.93; S4, 11 447.37+/-22215.44. Spearman's rank correlation analysis indicated a significant correlation between HBsAg level and liver inflammation stage (rs = -0.244) and fibrosis stage (rs = -0.365). ROC curve analysis of the diagnostic value of HBsAg for inflammation stages S more than or equal to 4 revealed that the area under the curve (AUC) was 0.70. The specificity of diagnosing S more than or equal to 4 was > 95.16% when HBsAg was less than or equal to 32995 IU/mL. Binary logistic regression analysis identified age, serum albumin, cholinesterase, and HBsAg as independent predictors of liver fibrosis.

CONCLUSIONHBsAg level is negatively correlated with liver inflammation and fibrosis stages for patients with CHB in the IC phase, and might represent a useful noninvasive marker of the degree of hepatic fibrosis.

Adult ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B, Chronic ; blood ; immunology ; pathology ; Humans ; Inflammation ; Liver ; immunology ; pathology ; Liver Cirrhosis ; immunology ; pathology ; Male ; Middle Aged ; Young Adult

Airway remodeling in asthma is a result of persistent inflammation and epithelial damage in response to repetitive injury. Recent studies have identified several important mediators associated with airway remodeling in asthma, including transforming growth factor-beta, interleukin (IL)-5, basic fibroblast growth factor, vascular endothelial growth factor, LIGHT, tumor necrosis factor (TNF)-alpha, thymic stromal lymphopoietin, IL-33, and IL-25. In addition, the epithelium mesenchymal transformation (EMT) induced by environmental factors may play an important role in initiating this process. Diagnostic methods using sputum and blood biomarkers as well as radiological interventions have been developed to distinguish between asthma sub-phenotypes. Human clinical trials have been conducted to evaluate biological therapies that target individual inflammatory cells or mediators including anti IgE, anti IL-5, and anti TNF-alpha. Furthermore, new drugs such as c-kit/platelet-derived growth factor receptor kinase inhibitors, endothelin-1 receptor antagonists, calcium channel inhibitors, and HMG-CoA reductase inhibitors have been developed to treat asthma-related symptoms. In addition to targeting specific inflammatory cells or mediators, preventing the initiation of EMT may be important for targeted treatment. Interestingly, bronchial thermoplasty reduces smooth muscle mass in patients with severe asthma and improves asthma-specific quality of life, particularly by reducing severe exacerbation and healthcare use. A wide range of different therapeutic approaches has been developed to address the immunological processes of asthma and to treat this complex chronic illness. An important future direction may be to investigate the role of mediators involved in the development of airway remodeling to enhance asthma therapy.
Airway Resistance/*immunology ; Asthma/immunology/*pathology/therapy ; Biological Therapy ; Cytokines ; Eosinophils ; Epithelium ; Humans ; Inflammation/immunology/*pathology/therapy ; Interleukin-5 ; Tumor Necrosis Factor-alpha

OBJECTIVETo investigate the effect of nuclear factor-kappaB (NF-kappaB) activation on the expression of proinflammatory cytokines in the lung tissues of rats with early-stage burn injury.

METHODSWistar rats were randomly divided into 3 groups, namely the normal control, burn, burn and PDTC treatment groups, and in the latter two groups, the rats were subjected to 35% TBSA full-thickness burns. Activation of pulmonary NF-kappaB at 1, 3, 6, 12, and 24 postburn hour (PBH) was tested by electrophoretic mobility shift assay , and the expressions of pulmonary tumor necrosis factor alpha (TNF alpha) and interleukin-8 (IL-8) mRNAs at 3, 6, 12, and 24 h were detected by RT-PCR.

RESULTSCompared to that of the control group, activity of pulmonary NF-kappaB in burned rats was markedly increased within 1 PBH and kept increasing till 24 h. Expressions of pulmonary TNF alpha and IL-8 mRNAs increased gradually, reaching the peak level at 6 PBH, and PDTC could effectively inhibit pulmonary NF-kappaB activation and expression of the pulmonary cytokines induced by the burn injury.

CONCLUSIONSevere burn injury may activate pulmonary NF-kappaB, which ultimately leads to secretion of cytokines in the lung tissues.

Animals ; Burns ; immunology ; pathology ; Disease Models, Animal ; Gene Expression ; Humans ; Inflammation Mediators ; immunology ; Interleukin-8 ; genetics ; immunology ; Lung ; immunology ; pathology ; NF-kappa B ; genetics ; immunology ; Random Allocation ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; genetics ; immunology

OBJECTIVE: The aim of this study was to explore the changes of the extracellular matrix in nasal mucosa by a guinea pig model of prolonged allergic-induced rhinitis. METHOD: Thirty-two male Hartley guinea pigs were randomly divided into four groups: allergen challenged groups (Group 2 w, Group 6 w and Group 12 w) and a control group. Ovalbumin-sensitized guinea pigs were repeatedly challenged with allergen twice a week from 2 weeks to 12 weeks. Matched control groups were challenged with physiological saline. Nasal mucosa were obtained from the animals killed. Hematoxylin-Eosin, Masson's trichrome, and immunohistochemical staining against transforming growth factor-beta1 (TGF-beta1), Collagen III and Collagen I were performed to nasal mucosa. RESULT: (1) Pathological examination showed obvious infiltration of eosinophils and the enlarged thickness of epithelial layer of nasal mucosa in the experiment groups. (2) The area ratios of blue stained in the extracellular matrix of nasal mucosa were increased. The area ratios of blue stained were statistically different in Group 6 w and Group 12 w compared with the control group. (3) The increasing absorbance of TGF-beta1 were statistically different in the experiment groups with the control group. The absorbance of Collagen III and Collagen I showed a rising trend along prolonged allergen challenged in the experiment groups. CONCLUSION Prolonged allergen challenge and the inflammation of nasal mucosa, can lead to the increasing of the inflammation relevant factors and the deposit of collagen in the extracellular matrix of nasal mucosa.
Allergens ; immunology ; Animals ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Eosinophils ; immunology ; Extracellular Matrix ; immunology ; metabolism ; pathology ; Guinea Pigs ; Inflammation ; Male ; Nasal Mucosa ; immunology ; metabolism ; pathology ; Rhinitis, Allergic, Perennial ; immunology ; metabolism ; pathology ; Transforming Growth Factor beta1 ; metabolism

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 probe the recovery mechanism of Zhenggu powder (ZGP) on acute soft tissue injury in cell levels.

METHODSForty rabbits which established animal model of acute soft tissue injury with hammer hitting,were divided randomly into normal group (A), model group (B), vaseline group (C)and ZGP group (D). Injured part was applied external drug daily after model was made. All animals were killed after using drug for 4 days. The local tissue of injured part was taken pathologic study, and was measured the content of IL-1beta, IL-6, TNFalpha by ELISA method and TXB2, 6-keto-PGF1alpha by RIA method.

RESULTSMuscular tissue of group A was normal. But that of group B and C was aberrant,such as swelling and broken of muscular fiber or infiltration of inflammatory cell. Such histological change of group D was lightly and hyperplasia of blood vessel was found. The contents of IL-1beta, TNFalpha, TXB2 and TXB2/6-keto-PGF1alpha in group D were lower than that of group B and group C. On the contrary, the contents of 6-keto-PGF1alpha in the group D were higher than that of group B and group C. The difference of content of IL-6 between groups was not obvious.

CONCLUSIONZGP could promote not only the dilution and the transportation of inflammatory cell factors,but also the repair and the regeneration of the injured tissue structures. The therapeutic effect of ZGP was not relative to IL-6.

Animals ; Cytokines ; immunology ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; Inflammation Mediators ; immunology ; Male ; Rabbits ; Random Allocation ; Soft Tissue Injuries ; drug therapy ; immunology ; pathology