Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to explore the effect of intratumour mutein VI-Hrec TNF-alpha administration upon the ultrastructural changes within the pulmonary tissue, with special attention paid to type II alveolar epithelial cells. The experiment was carried out on Buffalo rats with implantable Morris hepatoma series 5123 in the skeletal muscles of the limb. Mutein VI-Hrec TNF-alpha was administered in a dose of 10 micrograms once a day in a cycle of eight days. Control animals were given saline (PBS). Ultrastructural changes within the pulmonary tissue were evaluated in the electron transmission microscope (TEM), with special attention paid to alveolar epithelial cells. In the animals receiving hrec TNF-alpha mutein VI, damage to the alveolar epithelial cells was found. In the later period (14 days after the mutein treatment), repairing processes were observed, accompanied by intensified fibrotic processes in the interalveolar septal interstitium, with the subsequent pulmonary tissue rebuilding. The study confirmed the possibility of a peripheral action of hrec TNF-alpha mutein VI after its administration to the experimental Morris hepatoma and found the alveolar epithelial cells to be a key element of the pulmonary tissue subjected to the cytokine effect.
 ...
PMID:Alveolar epithelial cells after intratumour administration of HREC TNF-alpha mutein VI. 933 53

The aim of this study was to explore the effect of intratumor TNF-alpha administration upon the composition and adherence degree of cells isolated from the lungs through multiple bronchoalveolar lavages (BAL). Ultrastructural evaluation of BAL-isolated cells was performed in the scanning electron microscope (SEM). The experiment used Buffalo rats. A suspension of 3 x 10(6) cells of Morris hepatoma (5123 series) was injected to the right hind leg of the animals. After fourteen days, TNF-alpha was administered into the tumor in a dose of 1.5 x 10(4) U in 0.5 ml PBS solution. The animals of group I were given 4 doses of TNF-alpha and group II-8 doses of TNF-alpha every 24 hours. Control groups consisted of rats with injected Morris hepatoma which were given PBS solution instead of TNF-alpha (group III A, B) and animals without the hepatoma, given intramuscullary 4 or 8 TNF-alpha, respectively (groups IV A, B). No statistically significant differences were noticed between groups I and II with regard to the number of macrophages and neutrophils isolated from the rat lungs compared with control group IV. However, such differences were observed compared with group III. In group II and IV B, an increase in the adherence of isolated cells was found compared with group III, as well as arise in the number of macrophages with the largest diameters. We found a correlation between the increase in cell adherence and ultrastructural changes (in SEM) suggesting an increased activity of BAL-isolated cells.
 ...
PMID:Quantitative and morphological changes in BAL-isolated cells after the administration of TNF-alpha into Morris hepatoma. 933 55

The effect of repeated doses of TNF-alpha on the histological picture of the pulmonary tissue was analyzed in the present study. Special attention was paid to the lung rebuilding processes. TNF-alpha was applied intraperitoneally for two weeks in a dose of 10 micrograms/0.5 ml PBS/24h. Morphological analysis of the pulmonary tissue was performed after 1 and 28 days following the last TNF-alpha dose. The study revealed focal pulmonary tissue rebuilding with emphysema-like changes twenty eight days following termination of TNF-alpha administration. The rebuilding processes included interalveolar septal atrophy, collagen accumulation and damage-repair changes in type II alveolar epithelial cells. It has been demonstrated that apart from the protease-antiprotease hypothesis of the lung emphysema, the inflammatory-repair hypothesis should be considered. Both hypotheses are complementary to each other and interpret the emphysema-like changes as complications of various pathological conditions of the pulmonary tissue.
 ...
PMID:Tumor necrosis factor-alpha induces emphysema-like pulmonary tissue rebuilding. Changes in type II alveolar epithelial cells. 940 11

The immunomodulatory effects of the antibiotic sodium fusidate (SF) were tested in a model of T cell-dependent hepatic injury that can be induced in normal mice by a single i.v. injection of Con A. Signs of hepatitis with elevated transaminase activities in plasma, severe infiltration of the liver by neutrophil granulocytes, lymphocytes and monocytes, and necrotic areas were observed in control mice treated intraperitoneally with PBS 24 h and 1 h before Con A challenge. T cell- and macrophage-derived cytokines (IL-2, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha, IL-1beta, IL-6) were released with different kinetics in the circulation of these mice. SF, 20, 40 or 80 mg/kg, administered 24 h and 1 h before Con A challenge, protected the mice against the hepatitic effects of Con A. The protective effects of SF were dose-dependent and accompanied by profound modifications of blood levels of cytokines induced by Con A, so that, relative to control mice, SF (80 mg/kg)-treated animals showed markedly diminished plasma levels of IL-2, IFN-gamma and TNF-alpha, along with augmented levels of IL-6. These results suggest that SF might be useful in the treatment of immunoinflammatory liver diseases in humans.
 ...
PMID:Protection from concanavalin A (Con A)-induced T cell-dependent hepatic lesions and modulation of cytokine release in mice by sodium fusidate. 940 54

This study explores nasal administration of myelin basic protein (MBP) as a potential means of inducing tolerance to relapsing experimental autoimmune encephalomyelitis (PR-EAE), an experimental multiple sclerosis (MS) model that was induced in DA rats by immunization with rat spinal cord homogenate and incomplete Freund's adjuvant. DA rats received a total dosage of 0, 6, 60, 600 micrograms/rat of bovine MBP on ten consecutive days prior to immunization. EAE with typical course was observed in control rats receiving only PBS nasally, and in rats receiving 6 micrograms/rat of MBP. Rats receiving 60 micrograms/rat of MBP developed acute EAE but no relapse during 60 days of observation post immunization (p.i.). Only one of eight rats receiving 600 micrograms/rat of MBP developed slight, transient EAE. This protection was confirmed at the histology level and was associated with decreased levels of MBP-reactive IFN-gamma secreting Th1-like spleen cells on day 13 and 60 p.i. Rats receiving 60 and 600 micrograms/rat of MBP showed decreased serum anti-MBP IgG2b antibody levels on day 60 p.i., and rats receiving 600 micrograms/rat of MBP had marginally increased anti-MBP IgG1 antibody levels in serum compared to control EAE rats. Cytokine mRNA profiles in central nervous system (CNS) and spleen mononuclear cells were evaluated. Dose-dependent reduction of TNF-alpha mRNA expression were observed both in CNS and in splenocytes. Increased IL-4 and TGF-beta mRNA expression were observed in CNS of low (6 micrograms/rat) and median (60 micrograms/rat) dose of MBP tolerized rats and in splenocytes of rats tolerized with 600 micrograms/rat of MBP. We conclude that nasal administration of MBP in DA rat prevents EAE induced by immunization with whole rat spinal cord homogenate that, besides MBP, contains multiple antigenic myelin proteins. A mechanism involving MBP-reactive regulatory cells expressing IL-4 and TGF-beta mRNA acts as part in the induction of this tolerance.
 ...
PMID:Nasal administration of myelin basic protein prevents relapsing experimental autoimmune encephalomyelitis in DA rats by activating regulatory cells expressing IL-4 and TGF-beta mRNA. 941 60

To examine the effects of TNF-alpha on luteal functions, TNF-alpha was injected into the ovary of rabbits on the 7th day of pseudopregnancy (Day 7). The animals were laparotomized under general anesthesia, and 1 x 10(4) IU TNF-alpha dissolved in PBS was injected into the ovary. On Days 8 and 10, the blood progesterone (P) concentration was determined. The mean blood P level was 10.31 ng before the administration of TNF-alpha on Day 7. On Day 8, the mean blood P level was 11.22 ng in the control group, while it was markedly reduced to 1.29 ng in the TNF-alpha administration group. On Day 10, the mean blood P level was 6.80 ng in the control group and 5.49 ng in the TNF-alpha group. These results suggest that the capacity for P secretion of the corpus luteum, which reached a degenerative stage by TNF-alpha administration, can be recovered.
 ...
PMID:Effects of TNF-alpha injection into the ovary on blood progesterone concentration in pseudopregnant rabbits. 960 99

The innate immunity against murine cytomegalovirus (MCMV) at the early phase of infection is mediated by NK cells and macrophages. We studied the effects of hochu-ekki-to (HET), a traditional Chinese herbal medicine, on the regulation of innate immunity mediated by NK cells and macrophages. We found the oral administration of HET to increase both the number of leukocytes in the spleen and liver and the splenic NK cell cytotoxicity associated with the increased induction of serum IFN-alpha/beta after an MCMV infection but it had no effect on liver NK cells. However, no differences were found in the serum IL-12, IFN-gamma, TNF-alpha and nitric oxide (NO) production in the culture of macrophages between the HET- and PBS-treated mice on day 2 after MCMV infection. In addition, HET-treated splenic and peritoneal macrophages were found to show a higher intrinsic resistance against in vitro MCMV infection than that of PBS-treated mice. Therefore, the HET-induced effects on NK cells and macrophages selectively reduced the viral load in the spleen but not in the liver at an early phase of MCMV infection. HET may thus be useful in the treatment of human cytomegalovirus infection which commonly occurs in HIV-infected AIDS patients.
 ...
PMID:Protective effects of hochu-ekki-to, a Chinese traditional herbal medicine against murine cytomegalovirus infection. 1042 45

We tested the hypothesis that NO synthase inhibition alters proinflammatory cytokine expression during acute lung injury in mice. Five-week-old CD-1 mice were pretreated with l-NAME or d-NAME and then received an intratracheal injection of endotoxin (or PBS). TNF-alpha and IL-6 ELISAs and RT-PCR were performed on lung homogenates sampled 6 h later. l-NAME increased TNF-alpha and IL-6 protein and mRNA expression in lungs. Immunostaining demonstrated that TNF-alpha was expressed predominantly by macrophages in the lung. l-NAME did not alter pulmonary macrophage concentration. To better understand the effect of NO synthase inhibition, elicited murine peritoneal macrophages were stimulated in vitro with LPS after addition of l-NAME, d-NAME, nitroprusside, or control. Nuclear proteins were extracted 3 h later and electrophoretic mobility shift and supershift assays were performed using radiolabeled NF-kappaB consensus sequence oligonucleotides. Endotoxin increased NF-kappaB p50/p65 heterodimer binding. Binding was further increased by l-NAME and decreased by nitroprusside. The effect of nitroprusside was not blocked by guanylate cyclase inhibition. We conclude that, in endotoxin-induced acute lung injury, NO synthase inhibition increases proinflammatory cytokine protein and mRNA expression in part because NO decreases the amount of NF-kappaB available for binding to the regulatory region of proinflammatory cytokine genes.
 ...
PMID:Modulation of proinflammatory cytokines by nitric oxide in murine acute lung injury. 1043 Jul 48

The aim of the present study was the comparative analysis of morphological changes found in the lungs of Buffalo rats in the course of Morris hepatoma 5123 after i.t. treatment with recombinant human TNF-alpha (rhTNF-alpha) and its muteins. Modification of the native TNF-alpha molecule and synthesis of mutagenized analogues can prevent undesirable symptoms observed in the case of therapeutic administration of rhTNF-alpha. TNF-alpha has been shown to interact with two distinct membrane receptors (TNF-R): p55R and p75R. Mutagenized mutein V binds selectively with p55R. Mutein VI fails to recognize either TNF-R. The cytokines were applied in a dose of 10 micrograms protein in a cycle of 8 days. The control group consisted of tumor-bearing animals which were given PBS. Ultrastructural examinations were based on transmission electron microscope (TEM). Mutein VI-receiving animals showed enhanced changes of cytotoxic nature. Severe damage to endothelial cells (necrosis inclusive) was observed. Blood vascular lumen showed accumulation of neutrophils and monocytes. Features of enhanced activity of endothelial cells were noted. Focally, within pulmonary alveoli conglomerates of fibrin and fragments of damaged cells were found, with erythrocytes, neutrophils and macrophages in their vicinity. The epithelium of pulmonary alveoli showed signs of considerable damage, including necrosis. The lumen of pulmonary capillaries in rhTNF-alpha-treated animals showed a predominance of eosinophils and monocytic cells. Features of endothelial stimulation were observed, although without a tendency to form microthrombi. Much less pronounced changes both in the lung capillary bed and in the alveolar epithelial cells were noted in the mutein V-given animals. Our findings confirm the possibility of peripheral activation of cells involved in the cytokine-induced antitumor response. Mutein V with the smallest effect on the lung tissue rebuilding seems to be a rhTNF-alpha derivative which can delimit the undesirable symptoms in the course of antitumor therapy reduced to i.t. injections.
 ...
PMID:Comparative studies on the ultrastructure of the rat lungs after intratumor treatment of Morris hepatoma with rhTNF-alpha and its muteins. 1045 12

IL-18 expression has recently been detected in rheumatoid arthritis (RA) synovial membrane. We investigated the mechanisms by which IL-18-induced collagen-induced arthritis in DBA/1 mice primed intradermally with type II bovine collagen in IFA and boosted i.p. 21 days later with CII in saline. Mice were injected i.p. with rIL-12, rIL-18, or both (100 ng) during days -1 to 4 and again on days 20-24. Control mice received PBS. Mice treated with IL-12 or IL-18 alone developed significantly higher incidence and more severe disease compared with controls. These were elevated further by combination treatment with IL-12 and IL-18. The cytokine treatments led to markedly enhanced synovial hyperplasia, cellular infiltration, and cartilage erosion compared with controls. Cytokine-treated mice produced significantly more IFN-gamma, TNF-alpha, and IL-6 than the controls. Interestingly, IL-18-treated mice produced more TNF-alpha and IL-6, but less IFN-gamma, compared with mice treated with IL-12. Furthermore, splenic macrophages from DBA/1 mice cultured in vitro with IL-18, but not IL-12, produced substantial amounts of TNF-alpha. Mice treated with IL-18 or IL-18 plus IL-12 produced markedly more IgG1 and IgG2a anti-collagen Ab compared with controls, whereas IL-12 treatment only led to an enhanced IgG2a response. Together these results demonstrate that IL-18 can promote collagen-induced inflammatory arthritis through mechanisms that may be distinct from those induced by IL-12.
 ...
PMID:Combined effects of IL-12 and IL-18 on the induction of collagen-induced arthritis. 1084 7


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>