ISG15 is a well-known intracellular ubiquitin-like molecule involved in ISGylation. However, a recent study has revived the notion first put forward two decades ago that ISG15 is also a secreted molecule. Human neutrophils, monocytes and lymphocytes can release ISG15, even though this protein has no detectable signal peptide sequence. ISG15 has also been found in the secretory granules of granulocytes. The mechanism underlying ISG15 secretion is unknown. Secreted ISG15 acts on at least T and natural killer (NK) lymphocytes, in which it induces interferon (IFN)-gamma production. However, the mechanism by which ISG15 stimulates these cells also remains unclear. ISG15 and IFN-gamma seem to define an innate circuit that operates preferentially, but not exclusively, between granulocytes and NK cells. Inherited ISG15 deficiency is associated with severe mycobacterial disease in both mice and humans. This infectious phenotype probably results from the lack of secreted ISG15, because patients and mice with other inborn errors of IFN-gamma immunity also display mycobacterial diseases. In addition to raising mechanistic issues, the studies described here pave the way for clinical studies of various aspects, ranging from the use of recombinant ISG15 in patients with infectious diseases to the use of ISG15-blocking agents in patients with inflammatory diseases.
Amino Acid Sequence ; Animals ; Cytokines/chemistry/*secretion ; Humans ; Interferon-gamma/secretion ; Metabolism, Inborn Errors/metabolism ; Models, Biological ; Molecular Sequence Data

OBJECTIVETo study the effects of Aloe coarse polysaccharide on the levels of growth factors (EGF, TGF-alpha, TGF-beta1) and interleukins (IL-1beta, IL-6, IL-8) and tumor necrosis factor (TNF) in cultured keratinocytes.

METHODThe cultured keratinocytes were treated with Aloe coarse polysaccharide at concentrations of 75, 150, 300, 600, 1 200 mg x L(-1) land the equal volume of media as control group. The levels of EGF, TGF-alpha, TGF-beta1, IL-1beta, IL-6, IL-8 and TNF in the supernatants of cultured keratinocytes were assayed by enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA).

RESULTCompared with the control group, the levels of EGF, TGF-alpha, IL-1beta, IL-6 and IL-8 were significantly increased by treatment with Aloe coarse polysaccharide (P < 0.05, P < 0.01) and in a dose dependent manner, and the levels of TGF-beta1 and TNF were also increased but no statistical significance.

CONCLUSIONAloe coarse polysaccharide may promote keratinocytes to secrete EGF, TGF-alpha, IL-1beta, IL-6 and IL-8.

Aloe ; chemistry ; Cells, Cultured ; Cytokines ; secretion ; Dose-Response Relationship, Drug ; Epidermal Growth Factor ; secretion ; Humans ; Interleukin-1beta ; secretion ; Interleukin-6 ; secretion ; Interleukin-8 ; secretion ; Keratinocytes ; secretion ; Plants, Medicinal ; chemistry ; Polysaccharides ; administration & dosage ; isolation & purification ; pharmacology ; Transforming Growth Factor alpha ; secretion ; Transforming Growth Factor beta1 ; secretion ; Tumor Necrosis Factors ; secretion

In this study, we focused on the study of pharmacodynamic effects for 6 major bioactive lignans of Schisandra chinensis, namely deoxyschizandrin, schisandrin B, schisandrin C, schisandrin, schizandrol B and schisantherin A. A compound-gene-pathway network, which contained 124 related genes and 88 pathways, was constructed by collecting drug genes through mining relevant literatures and network pharmacology analysis. Based on the network analysis, 32 pathways and 80 related genes were associated with inflammation, which implied that anti-inflammatory might be the major pharmacodynamic effects of these compounds. All lignans except schizandrol B reduced LPS-induced NO production in RAW264.7 cells, which validated the anti-inflammatory hypothesis generated from network analysis. Furthermore, we investigated the effects of deoxyschizandrin, schisandrin C, schisandrin and schisantherin A on the secretion of inflammatory cytokines TNF-α, IL-1β, IL-6, PGE2 and protein expressions of iNOS, COX-2. As a result, deoxyschizandrin showed the strongest anti-inflammatory activity with inhibitory effect on all 4 inflammatory cytokines secretions and protein expressions of iNOS, COX-2. This study provided evidences for systematic exploration on the pharmacolgical actions and mechanisms of schisandra.
Animals ; Cells, Cultured ; Cytokines ; secretion ; Internet ; Lignans ; pharmacology ; Mice ; Schisandra ; chemistry

Dendritic cells have been known as a member of strong innate immune cells against infectious organelles. In this study, we evaluated the cytokine expression of splenic dendritic cells in chronic mouse toxoplasmosis by tissue cyst-forming Me49 strain and demonstrated the distribution of lymphoid dendritic cells by fluorescence-activated cell sorter (FACS). Pro-inflammatory cytokines, such as IL-1alpha, IL-1beta, IL-6, and IL-10 increased rapidly at week 1 post-infection (PI) and peaked at week 3 PI. Serum IL-10 level followed the similar patterns. FACS analysis showed that the number of CD8alpha+/CD11c+ splenic dendritic cells increased at week 1 and peaked at week 3 PI. In conclusion, mouse splenic dendritic cells showed early and rapid cytokine changes and may have important protective roles in early phases of murine toxoplasmosis.
Animals ; Antigens, CD11c/analysis ; Antigens, CD8/analysis ; Cytokines/*blood/*secretion ; Dendritic Cells/chemistry/*immunology ; Disease Models, Animal ; Flow Cytometry ; Mice ; Mice, Inbred BALB C ; Rodent Diseases/immunology ; Spleen/*immunology ; Time Factors ; Toxoplasmosis, Animal/*immunology

This study investigated whether elevated host immune capacity can inhibit T. gondii infection. For this purpose, we used silk protein extracted from Bombyx mori cocoons as a natural supplement to augment immune capacity. After silk protein administration to BALB/c mice for 6 weeks, ratios of T lymphocytes (CD4+ and CD8+ T-cells) and splenocyte proliferative capacities in response to Con A or T. gondii lysate antigen (TLA) were increased. Of various cytokines, which regulate immune systems, Th1 cytokines, such as IFN-gamma, IL-2, and IL-12, were obviously increased in splenocyte primary cell cultures. Furthermore, the survival of T. gondii (RH strain)-infected mice increased from 2 days to 5 or more days. In a state of immunosuppression induced by methylprednisolone acetate, silk protein-administered mice were resistant to reduction in T-lymphocyte (CD4+ and CD8+ T-cells) numbers and the splenocyte proliferative capacity induced by Con A or TLA with a statistical significance. Taken together, our results suggest that silk protein augments immune capacity in mice and the increased cellular immunity by silk protein administration increases host protection against acute T. gondii infection.
Animals ; Bombyx/*chemistry ; CD4-CD8 Ratio ; Cell Proliferation ; Cells, Cultured ; Cytokines/secretion ; Insect Proteins/*immunology ; Leukocytes, Mononuclear/immunology ; Male ; Mice ; Mice, Inbred BALB C ; Silk/immunology ; Spleen/immunology ; Survival Analysis ; Toxoplasma/*immunology/pathogenicity ; Toxoplasmosis, Animal/immunology/*prevention & control

OBJECTIVETo investigate the relationship between four cytokines in serum and prostatic fluid and chronic abacterial prostatitis (CAP).

METHODSThe levels of interleukin-2 (IL-2), IL-4, IL-8, tumor necrosis factor-alpha (TNF-alpha) were detected in 86 patients with CAP [CAP I (n = 60), WBC > or = 10/HP; CAP II (n = 26, WBC < 10/HP)], and 20 healthy males as control by ELISA.

RESULTSIL-2, IL-8 and TNF-alpha in serum and prostatic fluid, and IL-4 in serum in patients with CAP I were markedly higher than those in the control, respectively (P < 0.05 or P < 0.01). No significant difference was observed in IL-4 level in prostatic fluid among CAP I, CAP II and control groups respectively (P > 0.05), and in IL-2, IL4, TNF-alpha in serum and prostatic fluid between CAP II group and the control (P > 0.05). IL-8 was correlated with WBC number in prostatic fluid (r = 0.62, P < 0.05).

CONCLUSIONIL-2, IL-8, TNF-alpha may play roles in the process of pathogenesis of CAP, and they have applicable value in the diagnosis and typing of CAP.

Adult ; Bodily Secretions ; chemistry ; Chronic Disease ; Cytokines ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-2 ; metabolism ; Interleukin-4 ; metabolism ; Interleukin-8 ; metabolism ; Male ; Middle Aged ; Prostate ; secretion ; Prostatitis ; blood ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the anti-fibrosis mechanism of radix astragali through the observation on regulating cytokine secretion by astragalosides and astragalus polysaccharides in hepatic stellate cell line LX-2.

METHODSAstragalus polysaccharides and astragalosides at concentration of 25 microg/ml and 300 microg/ml were added to LX-2 cell culture.After 24 h culture total RNA contents were extracted and TGF-beta1, HGF, MP2 and MMP9 mRNA were measured by real time fluorescence quantification PCR technique. The cell growth curves were detected by Real Time Cell Electronics Sensing.

RESULTS300 microg/ml of astragalus polysaccharides suppressed LX-2 cell proliferation (P<0.05, in 94.7 h), while astragalosides induced an significant cell proliferation (P<0.05) both at lower and higher concentration. 25 microg/ml astragalus polysaccharides and astragalosides induced TGF-beta1 expression. For other cytokines, astragalus polysaccharides induced a 104.9 fold higher expression of MMP2, while astragalosides induced a 550.65 fold higher expression of IL-10. Astragalus polysaccharides at 300 microg/ml concentration exhibited an inhibition effect on TGF-beta1, HGF, MMP9 and IL-10 mRNA expression, while up-regulated MMP2 mRNA expression. Astragalosides at 300 mug/ml concentration inhibited TGF-beta1 mRNA expression, while up-regulated MMP2, MMP9 and IL-10 mRNA expression.

CONCLUSIONThe anti-fibrosis function of astragalus polysaccharides might be associated with up-regulation of MMP2 expression, while that of astragalosides with up-regulation of MMP2, MMP9 and IL-10 expression.

Astragalus membranaceus ; chemistry ; Cell Line ; Cytokines ; secretion ; Hepatic Stellate Cells ; cytology ; metabolism ; Humans ; Interleukin-10 ; genetics ; metabolism ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Plant Roots ; chemistry ; Polysaccharides ; isolation & purification ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Saponins ; isolation & purification ; pharmacology ; Triterpenes ; isolation & purification ; pharmacology ; Up-Regulation ; drug effects

OBJECTIVETo investigate the effect of Shengdi injection on rat model of lung inflammation.

METHODThe rat model was established by intratrachea instillation of lipopolysaccharides (LPS). The total and different white blood cell counts in bronchoalvoelar lavage fluid (BALF) were performed and the level of tumor necrosis factor-alpha (TNF-alpha), superoxide anion radical (O2-) and myeloperoxidase (MPO) was measured, as well as pathologic change of pulmonary tissue was tested.

RESULTShengdi injection could depress the increasing of the amount of total white blood cells and neutrophils and inhibit the increasing of TNF-alpha, O2-, MPO caused by LPS, as well as relieve the pathologic change including Neutrophils infiltrating and mucous edema in tracheae after intravenous administration. While it did not show the effect on monocyte, and histological lesion of the lung tissue.

CONCLUSIONShengdi injection shows some anti-inflammatory effect in rat lung induced by LPS and it can be concluded tentatively that anti-inflammatory, inhibiting the release of cytokine and inflammatory medium, and antioxidation are some of the mechanism of its effect on COPD.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; isolation & purification ; pharmacology ; Bronchoalveolar Lavage Fluid ; chemistry ; Cytokines ; secretion ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Injections, Intravenous ; Leukocyte Count ; Lipopolysaccharides ; Lung ; drug effects ; metabolism ; pathology ; Male ; Neutrophils ; drug effects ; pathology ; Peroxidase ; metabolism ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Pneumonia ; chemically induced ; metabolism ; prevention & control ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rehmannia ; chemistry ; Superoxides ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Many immune down-regulatory molecules have been isolated from parasites, including cystatin (cystain protease inhibitor). In a previous study, we isolated and characterized Type I cystatin (CsStefin-1) of the liver fluke, Clonorchis sinensis. To investigate whether the CsStefin-1 might be a new host immune modulator, we induced intestinal inflammation in mice by dextran sodium sulfate (DSS) and treated them with recombinant CsStefin-1 (rCsStefin-1). The disease activity index (DAI) increased in DSS only-treated mice. In contrast, the DAI value was significantly reduced in rCsStefin-1-treated mice than DSS only-treated mice. In addition, the colon length of DSS only-treated mice was shorter than that of rCsStefin-1 treated mice. The secretion levels of IFN-gamma and TNF-alpha in the spleen and mesenteric lymph nodes (MLNs) were significantly increased by DSS treatment, but the level of TNF-alpha in MLNs was significantly decreased by rCsStefin-1 treatment. IL-10 production in both spleen and MLNs was significantly increased, and IL-10+F4/80+ macrophage cells were significantly increased in the spleen and MLNs of rCsStefin-1 treated mice after DSS treatment. In conclusion, rCsStefin-1 could reduce the intestinal inflammation occurring after DSS treatment, these effects might be related with recruitment of IL-10 secreting macrophages.
Animals ; Antigens, Differentiation/analysis ; Clonorchis sinensis/*enzymology ; Colon/pathology ; Cystatins/*metabolism ; Cytokines/secretion ; Dextran Sulfate/toxicity ; Female ; Helminth Proteins/*metabolism ; Immunologic Factors/*metabolism ; Inflammation/chemically induced/*pathology ; Interleukin-10/analysis ; Intestines/*drug effects/pathology ; Lymph Nodes/immunology ; Macrophages/chemistry/*immunology ; Mice ; Mice, Inbred C57BL ; Severity of Illness Index ; Spleen/immunology