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Results for “Transforming Growth Factor beta2”

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At least 19 recordsLinked to original sources

PubMed2003

Heart and liver defects and reduced transforming growth factor beta2 sensitivity in transforming growth factor beta type III receptor-deficient embryos.

The type III transforming growth factor beta (TGFbeta) receptor (TbetaRIII) binds both TGFbeta and inhibin with high affinity and modulates the association of these ligands with their signaling receptors. However, the significance of TbetaRIII signaling in vivo is not known. In this study, we have sought to determine the role of TbetaRIII during development. We identified the predominant expression sites of TbetaRIII mRNA as liver and heart during midgestation and have disrupted the murine TbetaRIII gene by homologous recombination. Beginning at embryonic day 13.5, mice with mutations in TbetaRIII developed lethal proliferative defects in heart and apoptosis in liver, indicating that TbetaRIII is required during murine somatic development. To assess the effects of the absence of TbetaRIII on the function of its ligands, primary fibroblasts were generated from TbetaRIII-null and wild-type embryos. Our results indicate that TbetaRIII deficiency differentially affects the activities of TGFbeta ligands. Notably, TbetaRIII-null cells exhibited significantly reduced sensitivity to TGFbeta2 in terms of growth inhibition, reporter gene activation, and Smad2 nuclear localization, effects not observed with other ligands. These data indicate that TbetaRIII is an important modulator of TGFbeta2 function in embryonic fibroblasts and that reduced sensitivity to TGFbeta2 may underlie aspects of the TbetaRIII mutant phenotype.

Animals↗

PubMed2001

Expression profiles of endometrial leukemia inhibitory factor, transforming growth factor beta2 (TGFbeta2), and TGFbeta2 receptor in infertile bonnet monkeys.

The expression profiles of leukemia inhibitory factor (LIF), transforming growth factor beta2 (TGFbeta2), and transforming growth factor beta2 receptor (TGFbeta2R) were analyzed during the peri-implantation period in regularly menstruating, fertile bonnet monkeys and in animals in which endometrial nonreceptivity was induced by administering an antiprogestin, onapristone. Based on our previous experiences, a dose of 2.5 or 5 mg of onapristone was administered s.c. every third day during the menstrual cycle, because these dosages impair endometrial development without upsetting the normal gonadal endocrine profiles. Endometrial biopsy specimens were collected during the proliferative phase (estradiol levels about 200 pg/ml, n = 5) and peri-implantation period (Day 8 after midcycle peak in estradiol levels, n = 5) from normal ovulatory animals and during the peri-implantation period from onapristone-treated animals (n = 10). The biopsy specimens were processed to determine the expression patterns of LIF, TGFbeta2, and TGFbeta2R by immunohistochemical and reverse transcription-polymerase chain reaction (RT-PCR) methods. Levels of both protein and mRNA for LIF, TGFbeta2, and TGFbeta2R (analyzed by immunohistochemistry and RT-PCR, respectively) were greater in the endometrial samples collected during the peri-implantation period compared to samples collected during the proliferative phase in control animals. Treatment with either of the two doses (2.5 or 5 mg) of onapristone caused a significant (P < 0.05) down-regulation in the expression of LIF in the peri-implantation endometria. The endometrial expressions of TGFbeta2 and TGFbeta2R mRNAs were reduced significantly in animals treated with 5 mg of onapristone, but not in those treated with the lower dose. However, immunoreactive TGFbeta2 and TGFbeta2R proteins were significantly (P < 0.05) down-regulated in the endometrial samples from both the 2.5- and 5-mg-treated groups. The alterations observed in the expression patterns of LIF, TGFbeta2, and TGFbeta2R were specific, because the expression levels of epidermal growth factor receptor remained unaffected in the endometria from the treated groups. The present study demonstrates derangement in the expression profiles of LIF, TGFbeta2, and TGFbeta2R during the peri-implantation period in infertile bonnet monkeys. It may be hypothesized that TGFbeta2 function is one of the early steps in the regulation of the progesterone-driven cascade of events leading to endometrial receptivity, and that any aberration in this step may adversely affect the subsequent molecular events (i.e., expression of LIF). These data also suggest that potential aberrations in the functional network of locally produced cytokines and growth factors even may occur in an endometrium exposed to the optimal peripheral hormonal levels.

Animals↗

PubMed2000

The effects of topical transforming growth factor-beta2 and anti-transforming growth factor-beta2,3 on scarring in pigs.

BACKGROUND: Transforming growth factor-b2 (TGF-b2) has been implicated in the inflammatory response and subsequent scarring during wound healing. OBJECTIVE: The experiment was designed to study the effects of a topical application of TGF-b2 and mouse monoclonal anti-TGF-b2,3 neutralizing antibody (anti TGF-b2,3) on the development of fibrosis during healing. METHODS: Sixteen full-thickness excision wounds were made in the paravertebral and thoracic area of four domestic pigs. On day 0, three wounds each were treated with: a) 5 mg of TGF-b2, b) 5 mg of 2% methylcellulose (mc), or c) 1.2 mg of anti-TGF-b2,3. As a vehicle for treatment of each wound methylcellulose 2% was used. Four wounds served as the untreated air-exposed control. Wounds were biopsied and the tissue sectioned and stained with hematoxylin and eosin on days 7, 14, and 45. Three blinded observers evaluated the wound specimens. RESULTS: Using computer-aided point count stereology on days 7, 14, and 45, we found a statistically significant increase (p <.05) in the number of nucleated cells in the TGF-b2-treated wounds as compared to the other control wounds. Wounds treated with anti-TGF-b2,3 had significantly (p <.05) fewer nucleated cells on days 7,14, and 45. Microscopically, the TGF-b2-treated wounds had a larger scar area as compared to anti-TGF-b2,3 and controls. CONCLUSION: Treating wounds with an antibody directed against TGF-b2 might be a useful clinical approach to reduce fibrosis.

Administration, Topical↗

PubMed1998

A novel transforming growth factor beta2 antisense transcript in mammalian lung.

Transforming growth factor (TGF) beta2 gene expression was examined in murine, rat and human lung by in situ hybridization with riboprobes. Hybridization signal was observed in a variety of cells with the sense probe, and Northern-blot analysis with this probe demonstrated the presence of a novel 3.5 kb transcript. This first report suggesting the existance of a natural TGFbeta2 antisense transcript raises the possibility that such a transcript may play a role in regulating TGFbeta2 production.

Animals↗

PubMed2003

Transforming growth factor beta2 is released from PC12 cells via the regulated pathway of secretion.

Transforming growth factor beta2 (TGF-beta2), a prototypic member of a large superfamily of multifunctional cytokines, is expressed by neurons and glial cells. Its subcellular compartmentalization and release from neurons, however, are largely unknown. Here we show that TGF-beta2 colocalizes with the trans-Golgi network marker TGN38 and a marker molecule for secretory granules, chromogranin B (CgB), in PC12 cells. Similarly, primary hippocampal neurons show colocalization of TGN38 and TGF-beta2. A substantial amount of endogenous as well as transfected TGF-beta2 in PC12 cells comigrates with CgB on an equilibrium gradient, suggesting costorage in secretory granules. TGF-beta biological activity peaks in identical fractions. Depolarization of PC12 cells with high potassium triggers colocalization of CgB and TGF-beta2 at the cell surface, suggesting their regulated corelease from secretory granules. High potassium also liberates biologically active TGF-beta from PC12 cells and primary neurons. Our results indicate that a substantial portion of TGF-beta2 is secreted by the regulated secretory pathway in PC12 cells and hippocampal neurons.

Animals↗

PubMed1998

Transforming growth factor beta2 in the vitreous in proliferative diabetic retinopathy.

OBJECTIVE: To evaluate the hypothesis that transforming growth factor beta2 (TGF-beta2) is involved in the cause of proliferative diabetic retinopathy (PDR). METHODS: We assayed TGF-beta2 levels in the vitreous of patients with PDR and other vitreoretinal disorders. Forty-nine vitreous specimens were obtained from eyes of patients with PDR undergoing vitrectomy, and 19 vitreous specimens from nondiabetic subjects served as controls. We assessed TGF-beta2 levels using an enzyme-linked immunosorbent assay. Both mature and total TGF-beta2 levels were quantified. RESULTS: The mean (+/- SD) total levels of TGF-beta2 were 2634 (+/- 1652) pg/mL in the patients with PDR and 1305 (+/- 972) pg/mL in controls. The mean (+/- SD) levels of mature TGF-beta2 were 244 (+/- 316) pg/mL in patients with PDR and 79 (+/- 81) pg/mL in controls. Total and mature TGF-beta2 levels were significantly greater in patients with PDR (total TGF-beta2, P <.001; mature TGF-beta2, P <.01). Mature TGF-beta2 levels were higher in the vitreous of patients who had severe fibrous proliferation. CONCLUSION: The results indicate increased levels of both total and mature TGF-beta2 in the vitreous of patients with PDR, suggesting that TGF-beta2 plays an important role in the pathogenesis of PDR.

Diabetic Retinopathy↗

PubMed1999

Inhibition of glial scarring in the injured rat brain by a recombinant human monoclonal antibody to transforming growth factor-beta2.

The transforming growth factor-betas (TGF-betas) are potent fibrogenic factors implicated in numerous central nervous system (CNS) pathologies in which fibrosis and neural dysfunction are causally associated. In this study, we aim to limit the fibrogenic process in a model of CNS scarring using a recombinant human monoclonal antibody, derived from phage display libraries and specific to the active form of the TGF-beta2 isoform. The implicit inference of the work was that, as such antibodies are potential pharmacological agents for the treatment of human CNS fibrotic diseases, validation of efficacy in a mammalian animal model is a first step towards this end. Treatment of cerebral wounds with the anti-TGF-beta2 antibody led to a marked attenuation of all aspects of CNS scarring, including matrix deposition, formation of an accessory glial-limiting membrane, inflammation and angiogenesis. For example, in the wound, levels of: (i) the connective tissue components fibronectin, laminin and chondroitin sulphate proteoglycan; and (ii) wound-responsive cells including astrocytes and macrophages/microglia, were markedly reduced. Our findings suggest that such synthetic anti-fibrotic TGF-beta antibodies are potentially applicable to a number of human CNS fibrotic diseases to arrest the deposition of excessive extracellular matrix components, and maintain and/or restore functional integrity.

Animals↗

PubMed1999

Dynamics of protein 27 of avian leukosis virus and transforming growth factor beta2 in lymphoid leukosis susceptible and resistant broiler chicken breeding stock.

The dynamics of the serum concentration of protein 27 (P27) of avian leukosis virus and transforming growth factor beta2 (TGF-beta2) were compared during the period between 29 and 59 weeks of age in two flocks of broiler chicken breeding stock undergoing outbreaks of severe lymphoid leukosis (LL) associated with persistent high mortality (susceptible) and in another two flocks of breeding stock with the presence of avian leukosis virus in association with low mortality due to LL (resistant). The average mean concentration of serum P27 in the LL-susceptible flocks was significantly higher (p<0.05) than that in the LL-resistant flocks in six out of seven samplings performed at 5-week intervals, between 29 and 59 weeks of age. The peak in the average rise of serum P27 in the LL-resistant flocks (309 pg/ml) was associated with the highest level of TGF-beta2 (1282 pg/ml) among all flocks and at all sampling times. The significance of TGF-beta2 in inhibition of lymphoid tumour development is discussed.

Animals↗

PubMed2001

The release and activation of transforming growth factor beta2 associated with apoptosis of chick hypertrophic chondrocytes.

The apoptosis of hypertrophic chondrocytes at the interface between growth cartilage and invading vessels is at the center of a series of critical events in endochondral formation. We have shown that the hypertrophy and apoptosis of chick chondrocytes in culture is associated with the release and activation of transforming growth factor beta2 (TGF-beta2). Supplementation of the culture medium with agents that influenced the maintenance of hypertrophic differentiation also influenced the release of TGF-beta2. A large proportion of the TGF-beta2 released from the cells was shown to be in an active form-particularly TGF-beta2 associated with the support matrix. Inhibition of apoptosis with a broad-spectrum caspase inhibitor inhibited activation of the matrix-associated TGF-beta2. However, inhibition of apoptosis did not diminish the release of TGF-beta2. Release of TGF-beta2 by chondrocytes at a late stage of their terminal differentiation and its activation in association with apoptosis may provide a mechanism controlling the processes of vascular invasion of growth cartilage and the deposition of bone matrix on nearby cartilage remnants.

Animals↗

PubMed2001

Transforming growth factor beta2 induced pleurodesis is not inhibited by corticosteroids.

BACKGROUND: Talc and tetracyclines induce pleurodesis by directly injuring the pleura. The injury results in intense inflammation which subsequently leads to fibrosis. Corticosteroids can inhibit talc pleurodesis by reducing the inflammatory process. We hypothesised that transforming growth factor beta2 (TGFbeta2), a fibrogenic cytokine with immunomodulatory functions, could induce effective pleurodesis without generating significant pleural inflammation and therefore remain effective despite co-administration of corticosteroids. METHODS: Thirty rabbits were divided into two groups. Rabbits in the steroid group received weekly intramuscular injections of triamcinolone diacetate (0.8 mg/kg). Ten rabbits in each group were given 5.0 microg TGFbeta2 intrapleurally via a chest tube while the remaining five received 1.7 microg TGFbeta2. Pleurodesis was graded macroscopically after 14 days from 1 (none) to 8 (>50% symphysis). RESULTS: TGFbeta2 produced excellent pleurodesis at both 5.0 microg and 1.7 microg doses. The pleural effusions produced after the injection were low in all inflammatory markers. No significant differences were seen between the steroid group and controls in macroscopic pleurodesis scores (7.2 (1.3) v 7.1 (1.2)), levels of inflammatory markers in the pleural fluids (leucocyte 1107 (387)/mm(3) v 1376 (581)/mm(3); protein 3.1 (0.3) mg/dl v 2.9 (0.3) mg/dl, and LDH 478 (232) IU/l v 502 (123) IU/l), and the degree of microscopic pleural fibrosis and pleural inflammation. CONCLUSIONS: TGFbeta2 can induce effective pleurodesis and remains effective in the presence of high dose parenteral corticosteroids.

Animals↗

PubMed2002

Elevated transforming growth factor beta2 enhances apoptosis and contributes to abnormal outflow tract and aortic sac development in retinoic X receptor alpha knockout embryos.

Septation of the single tubular embryonic outflow tract into two outlet segments in the heart requires the precise integration of proliferation, differentiation and apoptosis during remodeling. Lack of proper coordination between these processes would result in a variety of congenital cardiac defects such as those seen in the retinoid X receptor alpha knockout (Rxra(-/-)) mouse. Rxra(-/-) embryos exhibit lethality between embryonic day (E) 13.5 and 15.5 and harbor a variety of conotruncal and aortic sac defects making it an excellent system to investigate the molecular and morphogenic causes of these cardiac malformations. At E12.5, before the embryonic lethality, we found no qualitative difference between wild type and Rxra(-/-) proliferation (BrdU incorporation) in outflow tract cushion tissue but a significant increase in apoptosis as assessed by both TUNEL labeling in paraffin sections and caspase activity in trypsin-dispersed hearts. Additionally, E12.5 embryos demonstrated elevated levels of transforming growth factor beta2 (TGFbeta2) protein in multiple cell lineages in the heart. Using a whole-mouse-embryo culture system, wild-type E11.5 embryos treated with TGFbeta2 protein for 24 hours displayed enhanced apoptosis in both the sinistroventralconal cushion and dextrodorsalconal cushion in a manner analogous to that observed in the Rxra(-/-). TGFbeta2 protein treatment also led to malformations in both the outflow tract and aortic sac. Importantly, Rxra(-/-) embryos that were heterozygous for a null mutation in the Tgfb2 allele exhibited a partial restoration of the elevated apoptosis and of the malformations. This was evident at both E12.5 and E13.5. The data suggests that elevated levels of TGFbeta2 can (1) contribute to abnormal outflow tract morphogenesis by enhancing apoptosis in the endocardial cushions and (2) promote aortic sac malformations by interfering with the normal development of the aorticopulmonary septum.

Animals↗

PubMed2002

Prominent expression of transforming growth factor beta2 gene in the chicken embryonic gonad as revealed by suppressive subtraction cloning.

cDNA cloning from chicken embryonic gonad subtracted from tissues of the brain, heart, liver, gizzard, mesonephros, and muscle was performed to identify growth factor genes with expression unique to embryonic ovary and testis. We obtained several cDNA clones encoding known and many unknown genes. We found for the first time that the transforming growth factor beta2 (TGF-beta2) is preferentially expressed in the chicken embryonic ovary and testis. cDNA subtraction cloning with respect to the selective expression of TGF-beta2 in the ovary and testis was further analyzed by reverse transcription-polymerase chain reaction analyses of other embryonic tissues. The ontogeny of TGF-beta2 was evaluated in chicken embryonic ovary and testis. In both testis and ovary, the levels of TGF-beta2 transcripts were high during the early period of embryonic development (E7), gradually decreased until the late embryonic days (E14--E17), and then slightly increased at the last embryonic day (E21). There was no difference in the TGF-beta2 transcripts per RNA between the left and the right ovaries. TGF-beta2 may have a critical role in the regulation of the development of chicken ovarian and testicular germ cells during the embryonic period.

Animals↗

PubMed2002

Localization of transforming growth factor beta2 (TGFbeta2) and its receptors, TbetaRI and TbetaRII, in uteri and blastocysts of the stripe-faced dunnart (Sminthopsis macroura) during gastrulation.

This study describes for the first time the spatial and temporal distribution of a growth factor and its receptors in uteri and conceptuses of a marsupial species during the peri-gastrulation period. Uteri (gravid and non-gravid) and blastocysts from 40 female stripe-faced dunnarts (Sminthopsis macroura) were collected over the peri-gastrula period (days 6.0-8.5) and stained immunohistochemically for transforming growth factor beta2 (TGFbeta2) and its receptors, TbetaRI and TbetaRII, to determine possible roles for TGFbeta2 in marsupial embryonic development. The events that occurred during the period examined included the appearance and proliferation of hypoblast and mesoderm, primitive streak and node formation, and early neurulation. Differences in TGFbeta2 quantities between gravid and non-gravid uteri reflect differences in uterine morphology, indicating a role for TGFbeta2 in endometrial remodelling. In blastocysts, large quantities of all three proteins in the trophectoderm during the node stage coincide with both blastocyst expansion before implantation and the appearance of multinucleated cells, indicating that TGFbeta2 plays a role in conceptus elongation and trophectoderm differentiation. In contrast, lack of TbetaRII in blastocysts during hypoblast formation and proliferation negates any role for TGFbeta2 in these processes, as both receptors are required for a response to TGFbeta2. High concentrations of TGFbeta2 but low concentrations of TbetaRII in blastocysts during early primitive streak formation indicate that paracrinal embryo-maternal signalling may be occurring, as blastocysts cannot respond to TGFbeta2 at this stage, but uteri could. A similar situation, but reversed, also occurs during primitive node formation.

Activin Receptors, Type I↗

PubMed2002

Transforming growth factor beta2 inhibits adipocyte differentiation induced by skeletal unloading in rat bone marrow stroma.

Skeletal unloading induced by hindlimb suspension in rats reduces bone formation and induces osteopenia, but its effect on adipogenesis is unknown. We assessed the effects of unloading and transforming growth factor (TGF) beta2 on bone marrow stromal cell adipocyte differentiation in relation with osteoblast differentiation. Skeletal unloading rapidly (4-7 days) decreased osteoblast transcription factor Runx2, osteocalcin (OC), and type I collagen messenger RNA (mRNA) levels and reduced bone formation in the long bone metaphysis. Conversely, unloading increased expression of the adipocyte transcription factor peroxisome proliferator-activated receptor gamma2 (PPARgamma2) at 4 days and increased expression of the adipocyte differentiation genes lipoprotein lipase (LPL) and aP2 in the bone marrow stroma at 7 days. Consistently, unloading increased the number and volume of adipocytes in the bone marrow stroma. Continuous (0-7 days) and late (4-7 days) treatments with TGF-beta2 corrected the abnormal expression of Cbfa1/Runx2, OC, and type I collagen mRNAs and normalized bone formation in unloaded metaphyseal bone. Moreover, both TGF-beta2 treatments decreased PPARy2 and C/EBPalpha mRNA levels at 4 days and normalized aP2 and LPL expression and adipocyte number and volume at 7 days. These results show that skeletal unloading increases adipocyte differentiation concomitantly with inhibition of osteoblast differentiation. These abnormalities are prevented and reversed by TGF-beta2, suggesting a role for TGF-beta in the control of adipogenic differentiation in the bone marrow stroma.

Adipocytes↗

PubMed1997

Antisense oligonucleotides specific for transforming growth factor beta2 inhibit the growth of malignant mesothelioma both in vitro and in vivo.

Transforming growth factor beta (TGF-beta) is a potent growth-regulatory and immunomodulatory cytokine that exerts a diverse range of effects on many types of cells. High levels of TGF-beta are produced by several human and mouse malignant mesothelioma (MM) cell lines, and it is known to act as a growth factor for these cells. Antisense oligonucleotides (ODNs), targeted against specific TGF-beta mRNA, were used to block TGF-beta production from MM cells in vitro and in vivo. TGF-beta antisense ODNs were encapsulated in liposomes and transfected into MM cells or delivered intratumorally. TGF-beta2 mRNA levels, assessed by semiquantitative PCR, and TGF-beta2 protein secretion were reduced after TGF-beta2 antisense ODN transfection. MM cell proliferation, assessed by tritiated thymidine uptake, was specifically inhibited by both TGF-beta1- and TGF-beta2-specific antisense ODNs. In vivo administration of TGF-beta2 antisense ODNs, delivered locally, reduced tumor growth. These data show that the blockade of TGF-beta2 within this tumor reduces tumor growth and raises the possibility that TGF-beta2 antisense ODNs may be useful as a therapy for this disease.

Animals↗

PubMed2002

Soluble Fas ligand and transforming growth factor beta2 in the aqueous humor of patients with endothelial immune reactions after penetrating keratoplasty.

BACKGROUND: Excellent long-term prognosis of penetrating corneal grafts has been explained by the immunological privilege of the cornea and the anterior chamber. In animal models the secretion of transforming growth factor beta(2) (TGF-beta(2)) into the anterior chamber and the expression of the Fas ligand on corneal endothelial cells were identified as important for the integrity of the immunological privilege. OBJECTIVE: To determine the TGF-beta(2) and soluble Fas ligand (sFasL) levels in the aqueous humor of patients after penetrating keratoplasty (PK) who have and who do not have immune reactions. METHODS: Anterior chamber puncture was performed in 13 patients who had a cataract without PK (group 1), in 31 patients after PK who did not have immune reactions (group 2), and in 12 patients after PK newly diagnosed as having endothelial immune reactions (group 3). Total TGF-beta(2) and sFasL were determined via enzyme-linked immunosorbent assay. RESULTS: Transforming growth factor beta(2) was detected in all patients, irrespective of the underlying condition; there was no difference in TGF-beta(2) levels between the different groups (P =.89, analysis of variance). None of the patients in group 1, 11 of 31 patients in group 2, and 8 of 12 patients in group 3 had detectable sFasL concentrations (P =.002, chi(2) test). Soluble Fas ligand averaged (mean [SD]) 20.8 (31.1) pg/mL in group 2, and 38.1 (33.2) pg/mL (P<.01, analysis of variance) in group 3. CONCLUSIONS: It appears that total TGF-beta(2) is maintained at high steady-state levels, while the level of sFasL is up-regulated in patients who underwent PK, particularily in the advent of graft rejection.

Aged↗

PubMed2003

Association of INOS, TRAIL, TGF-beta2, TGF-beta3, and IgL genes with response to Salmonella enteritidis in poultry.

Several candidate genes were selected, based on their critical roles in the host's response to intracellular bacteria, to study the genetic control of the chicken response to Salmonella enteritidis (SE). The candidate genes were: inducible nitric oxide synthase (INOS), tumor necrosis factor related apoptosis inducing ligand (TRAIL), transforming growth factor beta2 (TGF-beta2), transforming growth factor beta3 (TGF-beta3), and immunoglobulin G light chain (IgL). Responses to pathogenic SE colonization or to SE vaccination were measured in the Iowa Salmonella response resource population (ISRRP). Outbred broiler sires and three diverse, highly inbred dam lines produced 508 F1 progeny, which were evaluated as young chicks for either bacterial load isolated from spleen or cecum contents after pathogenic SE inoculation, or the circulating antibody level after SE vaccination. Fragments of each gene were sequenced from the founder lines of the resource population to identify genomic sequence variation. Single nucleotide polymorphisms (SNP) were identified, then PCR-RFLP techniques were developed to genotype the F1 resource population. Linear mixed models were used for statistical analyses. Because the inbred dam lines always contributed one copy of the same allele, the heterozygous sire allele effects could be assessed in the F1 generation. Association analyses revealed significant effects of the sire allele of TRAIL-StyI on the spleen (P <0.07) and cecum (P <0.0002) SE bacterial load. Significant effects (P <0.04) were found on the cecum bacterial load for TGF-beta3-BsrI. Varied and moderate association was found for SE vaccine antibody response for all genes. This is the first reported study on the association of SNP in INOS, TRAIL, TGF-beta2, TGF-beta3, and IgL with the chicken response to SE. Identification of candidate genes to improve the immune response may be useful for marker-assisted selection to enhance disease resistance.

Animals↗

PubMed1996

Tumor necrosis factor alpha enhances secretion of transforming growth factor beta2 in MCF-7 breast cancer cells.

We studied the effect of tumor necrosis factor alpha (TNF-alpha) on transforming growth factor beta (TGF-beta) secretion by human breast cell lines to further characterize the antitumor effects of TNF-alpha. We found that TNF-alpha increased the secretion of TGF-beta in two established breast cancer cell lines (MCF-7 and ZR-75-1) but not in two immortalized human mammary epithelial cell lines (184B5 and MCF-10A). In MCF-7 cells, TNF-alpha increased the secretion of total TGF-beta 6.1-fold within 72 h in a dose-dependent manner. The secretion of both latent and active forms of TGF-beta was increased, and their ratio altered from 25:1 to 12:1 in the medium. TNF-alpha converted the secretory pattern of TGF-beta by MCF-7 cells from the heterodimeric form TGF-beta1.2 to the homodimeric form TGF-beta2. Immunoblot analysis under nonreducing conditions identified four molecular mass species of TGF-beta secreted in the culture media of untreated MCF-7 cells (238, 210, 40-55, and 25 kDa). Under reducing conditions, three molecular mass species of TGF-beta were identified: 88, 44, and 12 kDa. Gel filtration analysis demonstrated that the secreted TGF-beta within the range of 12-88 kDa was biologically active. TNF-alpha treatment did not alter the size of molecular mass species secreted by MCF-7 cells and did not change steady-state levels of mRNA for TGF-beta1 or TGF-beta2. These findings indicate that TNF-alpha may regulate quantitatively and qualitatively TGF-beta secretion by human breast cancer cells in vitro. The diverse biological activities of TGF-beta may also allow TNF-alpha to regulate the growth and metabolism of human mammary epithelial cells and/or stromal cells in a paracrine manner.

Breast Neoplasms↗