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

Glucocorticoids are known to decrease wound healing by inhibiting the inflammatory response and collagen synthesis. In patients on steroids requiring emergency surgery, a safe agent that can be administered systemically is needed to reverse the deleterious effects of corticosteroids. TGF-beta and PDGF work topically but are not candidates for systemic administration. IGF-I and IGF-I:BP-3 are logical choices for systemic administration to improve wound healing. Both have been found in our laboratory to repair the corticosteroid-induced defect in wound healing when applied topically; the IGF-I:BP-3 complex gave significantly better results than IGF-I alone. Therefore, we asked whether these agents administered systemically could reverse the impaired wound healing caused by corticosteroids and whether the IGF-I:BP-3 complex was superior. Sprague-Dawley rats 350 g had 4 Hunt-Schilling wire mesh wound cylinders implanted s.c. on the back. Depo-Medrol (8 mg) was given s.c. at the time of surgery. Experimental rats were given daily s.c. injections of IGF-I or IGF-I:BP-3 (supplied by Celtrix Pharm, Santa Clara, CA) in PBS and 0.1% rat serum albumin, pH 6.0. The groups were: vehicle; IGF-I 125 micrograms/d; IGF-I:BP-3 complex containing 125 micrograms IGF-I/d. On post-op. day 17, the tissue in the wound cylinders was harvested and dried at 37 degrees C. Dry weight, DNA, total protein, and hydroxyproline (collagen) contents were obtained by our published procedures. Wound cylinder dry weight, DNA, total protein and hydroxyproline were increased by IGF-I 250%, 340%, 200% and 205%, respectively, over controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo effects of systemic insulin-like growth factor-I alone and complexed with insulin-like growth factor binding protein-3 on corticosteroid suppressed wounds. 768 31

The effect of IL-4, IL-10, and TGF-beta on expression of procoagulant activity (PCA) and of surface-associated tissue factor (TF) by human monocyte-derived macrophages was determined. Monocytes were allowed to mature to macrophages in teflon bags, and were primed either in suspension cultures, or after subculturing in microtiter plates. PCA was determined in PBS-stimulated cells (constitutive PCA) or after stimulation with LPS for 6 hr. TGF-beta significantly reduced constitutive and LPS-induced PCA. This effect was associated with a reduction in surface-expressed TF, but was not correlated with TNF-alpha production in LPS-stimulated cells. The TGF-beta effect was seen both in suspension cultures and in adherent cultures. IL-10 strongly down-regulated LPS-induced PCA, an effect closely correlated with TNF production. It had a weaker, albeit significant effect on constitutive PCA, when tested on suspended cells, and PCA down-regulation was associated with reduction in TF surface expression. IL-4 reduced neither constitutive nor induced PCA in macrophages, and had little effect on TF surface expression, although it strongly down-regulated CD14 expression. Also in monocytes, IL-4 influenced TF expression to a lesser degree than IL-10 and TGF-beta. In the monocytoid cell line, THP-1, PCA/TF was down-regulated preferentially by TGF-beta. Our findings point to a complex cytokine-mediated regulation of PCA at the level of TF expression and possibly at additional levels.
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PMID:Transforming growth factor-beta and interleukin-10, but not interleukin-4, down-regulate procoagulant activity and tissue factor expression in human monocyte-derived macrophages. 790 94

Nasal administration of nicotinic acetylcholine receptor (AChR) to Lewis rats prior to myasthenogenic immunization with AChR plus Freund's complete adjuvant (FCA) resulted in prevention or marked decrease of the severity of EAMG, suppression of AChR-specific B cell responses and of AChR-reactive T cell functions. To examine the involvement of immunoregulatory cytokines and the underlying mechanisms involved in tolerance induction, in situ hybridization with radio-labelled synthetic oligonucleotide probes was adopted to enumerate mononuclear cells (MNC) expressing mRNA for the proinflammatory cytokine IFN-gamma, the B cell stimulating IL-4 and the immune response-down-regulating TGF-beta. Popliteal and inguinal lymph nodes from EAMG rats contained elevated numbers of AChR-reactive IFN-gamma, IL-4 and TGF-beta mRNA-expressing cells compared with control rats receiving PBS nasally and injected with FCA only. Nasal tolerance to EAMG was accompanied by decreased numbers of AChR-reactive IFN-gamma and IL-4 mRNA-expressing cells, and strong up-regulation of TGF-beta mRNA-positive cells in lymphoid organs compared with non-tolerized EAMG control rats. The relative affinity of anti-AChR antibodies was lower, but muscle AChR amounts were higher in nasally tolerized rats compared with non-tolerized EAMG control rats. The results suggest that IFN-gamma and IL-4 are central effector molecules in the development of EAMG, and that TGF-beta plays an important role in tolerance induction to EAMG.
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PMID:Cellular mRNA expression of interferon-gamma (IFN-gamma), IL-4 and transforming growth factor-beta (TGF-beta) in rats nasally tolerized against experimental autoimmune myasthenia gravis (EAMG). 909 37

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.
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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

Endoglin (CD105), which is a component of the TGF-beta receptor complex, is highly expressed at the surface of proliferating human endothelial cells such as those of tumor vessels. In the present study, we tested the antitumor efficacy of (125)I-labeled anti-endoglin monoclonal antibodies (MAbs), SN6f and SN6j, against s. c. tumors of MCF-7 human breast cancer cells in SCID mice by i.v. administration. SN6f and SN6j cross-react weakly with mouse endothelial cells, but show no significant reactivity with MCF-7 tumor cells. These MAbs are effectively internalized into the cells after binding to the cell surface antigen of endothelial cells. Four groups of SCID mice (n = 10 or 9 in each group) inoculated s.c. with 8 x 10(6) MCF-7 cells were treated with (125)I-SN6f (10 microCi), (125)I-SN6j (10 microCi), a (125)I-labeled isotype-matched control IgG (10 microCi) or PBS. The systemic therapy was performed in 2 series, i.e., on days 3, 5, 7 and days 58, 60, 62. Both (125)I-SN6f and (125)I-SN6j showed significant growth suppression of the tumors, whereas the (125)I-labeled control IgG did not show any significant antitumor efficacy. No significant toxicity or weight loss was observed in mice treated with either (125)I-SN6f or (125)I-SN6j. After 100 days of observation, autopsies revealed no significant organ damage. Our results show the possible usefulness of antiangiogenic radioimmunotherapy using (125)I-labeled anti-endoglin MAbs.
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PMID:Antiangiogenic radioimmunotherapy of human solid tumors in SCID mice using (125)I-labeled anti-endoglin monoclonal antibodies. 1041 73

In a previous study, we found that the CSF level of transforming growth factor beta 1 (TGF-beta 1) is elevated following subarachnoid hemorrhage (SAH) in patients who later develop communicating hydrocephalus, while in mice, an intrathecal injection of TGF-beta 1 can induce communicating hydrocephalus. Recently, histopathological changes in the leptomeninges were studied using the above TGF-beta 1 induced mice model of hydrocephalus. In the present study, in order to further clarify the ventricular dilatation mechanism, we examined cerebrospinal fluid (CSF) flow dynamics in TGF-beta 1 induced hydrocephalic mice. To assess CSF flow, Indian ink was injected into the passage pathway and the time taken for the ink to pass from the parietal intrameningeal CSF space to cervical lymph nodes was determined. The ink study revealed a significant lengthening of the ink passage time due to altered CSF flow dynamics, while a histological examination showed ink stasis in the altered leptomeningeal CSF space compared to PBS injected control mice. TGF-beta 1 induced increased cellularity in the leptomeninx and fibrosis, and a subsequent narrowing of the intrameningeal CSF space. This narrowing causes a disturbance in CSF flow, thus generating a mild pressure gradient, which ultimately leads to the development of slowly progressive ventricular dilatation. After SAH, elevated TGF-beta 1 in the CSF may play a similar role, in concert with other factors, in the development of communicating hydrocephalus in human.
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PMID:Study of cerebrospinal fluid flow dynamics in TGF-beta 1 induced chronic hydrocephalic mice. 1076 13

We have studied the effects of treatment with recombinant human (rh)IL-6 on clinical, histological and immunological parameters of protracted relapsing (PR) experimental allergic encephalomyelitis (EAE) in DA rats. rhIL-6 (50 microg/rat subcutaneously/day) was given under three different regimens, as early prophylaxis, from 1 day prior to 14 days after immunization, in late prophylaxis, from day +7 until day 21 post-immunization (p.i.) and therapeutically to rats with clinical signs of EAE from day 14 to day 28 p.i. Although rhIL-6 failed to modulate the course of PR-EAE when administered as the early prophylactic regimen, it exerted clear-cut favourable effects on the course of the disease if was administered either as later prophylactic or as therapeutic treatment. Under these conditions, rhIL-6 accelerated recovery from EAE attacks and reduced/milded subsequent EAE episodes as compared to either PBS- or heat-inactivated rhIL-6-treated control rats. In agreement with this clinical effect, relative to PBS-treated rats, the animals injected with rhIL-6 exhibited lower numbers of MHC class II(+) and CD4(+) cells in their spinal cords. rhIL-6-treatment also profoundly modulated the endogenous cytokine network, the treated rats displaying increased numbers of spleen cells expressing mRNA transcripts of the anti-inflammatory cytokines IL-10 and TGF-beta along with simultaneously reduced numbers of mRNAs for TNF-alpha. In addition, upon ex vivo exposure to either myelin basic protein peptide 63-88 (MBP63-88) or to phytoaemagglutinin A, the numbers of IFN-gamma secreting splenocytes was also significantly reduced (ELISPOT analysis) in rhIL-6-treated rats as compared to PBS-treated controls.
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PMID:Curative effects of recombinant human Interleukin-6 in DA rats with protracted relapsing experimental allergic encephalomyelitis. 1143 71

Recent studies suggest that human adipose tissue contain pluripotent cells similar to bone marrow-derived stromal cells (BSCs). Taking advantage of homogeneously marked cells from green fluorescent protein (GFP) transgenic mice, we have previously demonstrated that BSCs differentiate into a variety of cell lineages both in vitro and in vivo). In the present study, we extend this approach to characterize adipose-derived stromal cells (ASCs)). These cells derived from human are sometimes called processed lipoaspirate (PLA) cells. ASCs were prepared from inguinal fat pads of GFP transgenic mice after extensive washing with PBS and treatment with collagenase. After the primary culture in control medium (DMEM + 10% FBS), the cells were incubated in either chondrogenic medium (DMEM + 1% FBS + insulin + ascorbate 2-phosphate + TGF-beta 1) or osteogenic medium (DMEM + 10%FBS + dexamethasone + ascorbate-2-phosphate + beta-glycerophosphate) for two to four weeks. Chondrogenic differentiation was assessed by Alcian blue staining, while osteogenic differentiation was by von Kossa and Alkaline phosphatase staining. ASCs incubated in chondrogenic medium induced Alcian blue positive cells. Incubation with osteogenic medium became positive for von Kossa and Alkaline phosphatase staining. No osteochondrogenic differentiation was observed in cells incubated with control medium. This cell population can be easily identified through fluorescence microscope, it should be an ideal source of ASCs for further experiments of stem cell biology and tissue engineering.
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PMID:Chondrogenic and osteogenic differentiation of adipose-derived stem cells isolated from GFP transgenic mice. 1532 83

Recent studies of murine models of mucosal inflammation suggest that, whereas some kinds of bacterial microflora are inducers of disease, others, known as probiotics, prevent disease. In the present study, we analyzed the regulatory cytokine and cell response to probiotic (VSL#3) administration in the context of the Th1 T cell colitis induced by trinitrobenzene sulfonic acid treatment of SJL/J mice. Daily administration of probiotics for 3 wk to mice during a remission period between a first and second course of colitis induced by trinitrobenzene sulfonic acid, resulted in a milder form of recurrent colitis than observed in mice administered PBS during this same period. This protective effect was attributable to effects on the lamina propria mononuclear cell (LPMC) population, because it could be transferred by LPMC from probiotic-treated mice to naive mice. Probiotic administration was associated with an early increase in the production of IL-10 and an increased number of regulatory CD4+ T cells bearing surface TGF-beta in the form of latency-associated protein (LAP) (LAP+ T cells). The latter were dependent on the IL-10 production because administration of anti-IL-10R mAb blocked their appearance. Finally, the LAP+ T cells were essential to the protective effect of probiotics because administration of anti-IL-10R or anti-TGF-beta at the initiation of recurrent colitis induction or depletion of LAP+ T cells from LPMC abolished the latter's capacity to transfer protection to naive recipients. These studies show that probiotic (VSL#3) administration during a remission period ameliorates the severity of recurrent colitis by inducing an immunoregulatory response involving TGF-beta-bearing regulatory cells.
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PMID:Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells. 1574 54

The present study investigated the role of IL-10 produced by the mesangial cells in postnephrectomy compensatory renal growth and the effect of the immunomodulator AS101 on this process. One hundred forty unilateral nephrectomized and sham-operated male Sprague-Dawley rats were treated by AS101 or PBS before and after surgery. The results show that secretion of IL-10 and TGF-beta by mesangial cells isolated from the remaining kidneys was increased significantly, compared with those of control and sham animals. Moreover, TGF-beta secretion by mesangial cells was increased after the addition of exogenous recombinant IL-10 and inhibited in the presence of neutralizing anti-IL-10 antibodies. In vivo, compensatory growth of the remaining kidneys was associated with significant increase in IL-10 content in renal tissues and plasma. Immunohistochemical studies show that IL-10 was produced by mesangial cells. Elevated IL-10 levels were followed by the rise in TGF-beta content in plasma and renal tissue. AS101 treatment decreased IL-10 and TGF-beta expression in plasma and kidney tissues and results in 25% reduction in the fresh and fractional kidney weight and decreased hypertrophy of tubular cells (protein/DNA ratio, morphometric analysis). Taken together, these data demonstrate that TGF-beta production by mesangial cells is IL-10 dependent. Mesangial cells are the major source of IL-10 in kidneys. AS101, by inhibiting the activity of IL-10, decreases TGF-beta production by mesangial cells, thus limiting compensatory tubular cell hypertrophy.
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PMID:Mesangial cells initiate compensatory renal tubular hypertrophy via IL-10-induced TGF-beta secretion: effect of the immunomodulator AS101 on this process. 1657 92


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