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Thioredoxin (TRX) is a redox regulating protein which has protective effects against oxidative stress-induced damage to cells and tissues. In this study, we investigated the effects of orally administered TRX derived from edible yeast, Saccharomyces cerevisiae, on gastric mucosa. First, we examined the digestibility of orally administered yeast TRX in mice, and detected yeast TRX in the stomach for 4 h after administration. Next, we investigated the mitigation of gastric mucosal injury after the oral administration of yeast TRX in water-immersion restraint stress and HCl/ethanol-induced gastric ulcer models. Furthermore, we conducted DNA microarray analysis, using the HCl/ethanol-induced model, which revealed that several groups of genes related to tissue repair were upregulated in ulcer regions in the stomachs of rats administered with yeast TRX. These results demonstrated the viability of the use of oral administrations of yeast TRX to protect the gastric mucosa.

Thioredoxin (TRX) catalyzes the reduction of disulfide bonds in proteins via the NADPH-dependent thioredoxin reductase system. Reducing the disulfide bonds of allergenic proteins in food by TRX lowers the allergenicity. We established in this study a method to prepare TRX-enriched extracts from the edible yeast, Saccharomyces cerevisiae, on a large and practical scale, with the objective of developing TRX-containing functional foods to mitigate food allergy. Treating with the yeast TRX-enriched extracts together with NADPH and yeast thioredoxin reductase enhanced the pepsin cleavage of β-lactoglobulin and ovomucoid (OM). We also examined whether yeast TRX can mitigate the allergenicity of OM by conducting immediate allergy tests on guinea pigs. The treatment with TRX reduced the anaphylactic symptoms induced by OM in these tests. These results indicate that yeast TRX was beneficial against food allergy, raising the possibility that yeast TRX-enriched extracts can be applied to food materials for mitigating food allergy.

The feeding-fasting nutritional transition triggers a dynamic change in metabolic pathways and is a model for understanding how these pathways are mutually organized. The targeted disruption of the thioredoxin binding protein-2 (TBP-2)/thioredoxin-interacting protein (Txnip)/VDUP1 gene in mice results in lethality with hypertriglyceridemia and hypoglycemia during fasting. To investigate the molecular mechanism of the nutritional transition and the role of TBP-2, microarray analyses were performed using the liver of TBP-2(-/-) mice in the fed and fasted states. We found that the fasting-induced reduction in the expression of lipogenic genes targeted by insulin (SREBP-1), such as FASN and THRSP, was abolished in TBP-2(-/-) mice, and the expression of lipoprotein lipase is down-regulated, which was consistent with the lipoprotein profile. TBP-2(-/-) mice also exhibited enhanced glucose-induced insulin secretion and sensitivity. Another feature of the hepatic gene expression in fed TBP-2(-/-) mice was the augmented expression of peroxisome proliferator activated receptor (PPAR) target genes, such as CD36, FABP2, ACOT1, and FGF21, to regulate fatty acid consumption. In TBP-2(-/-) mice, PPARalpha expression was elevated in the fed state, whereas the fasting-induced up-regulation of PPARalpha was attenuated. We also detected an increased expression of PPARgamma coactivator-1alpha protein in fed TBP-2(-/-) mice. TBP-2 overexpression significantly inhibited PPARalpha-mediated transcriptional activity induced by a specific PPARalpha ligand in vitro. These results suggest that TBP-2 is a key regulator of PPARalpha expression and signaling, and coordinated regulation of PPARalpha and insulin secretion by TBP-2 is crucial in the feeding-fasting nutritional transition.

Oxidative stress occurs where there is an imbalance between the production and scavenging of free radicals. Pregnancy per se is a state of oxidative stress due to the increased metabolic activity of placental mitochondria and reduced scavenging ability of antioxidant systems. Overproduction of reactive oxygen species may be associated with impaired fetal growth. However, the physiological influence of antioxidant systems on fetal growth is not well understood. In this study we assessed the effects of antioxidant systems on fetal growth using human thioredoxin (hTRX)-1 overexpressing transgenic (Tg) mice. Tg or C57BL/6 [wild-type (WT)] male mice were mated with WT female mice, and dams were killed to obtain the fetuses and placentas on gestational d 15. Tg fetuses were significantly heavier than WT fetuses, whereas placental weight did not differ significantly between the two groups. Immunohistochemically, hTRX-1 was localized to the nuclei of labyrinthine trophoblasts in Tg mice. In addition, placental expression of 8-hydroxy-2'-deoxyguanosine, which reflects DNA damage caused by oxidative stress, was reduced in Tg mice compared with WT mice. Placental expression of glucose transporter-1 mRNA and protein was significantly higher in Tg mice than WT mice, whereas no significant differences were observed for glucose transporter-3, IGF, and IGF-binding protein mRNA expression. These results suggest that placental and/or systemic antioxidant systems can influence fetal growth. In particular, increased hTRX-1 activity and the resulting modified placental redox state may play an important role in fetal growth by increasing the availability of glucose.

Background: Oxidative stress has been suggested to play an important role in the pathogenesis of diabetic nephropathy. In the present study, the effects of thioredoxin1 (TRX1) overexpression, a small protein with antioxidant property, on the development of diabetic nephropathy in streptozotocin-induced diabetic animals were investigated using TRX1 transgenic mice (TRX1-Tg)., Methods: Eight-week-old male TRX1-Tg and wild-type mice littermates (WT) mice were treated either with streptozotocin (200 mg/kg) or vehicle alone. After 24 weeks of treatment, diabetic nephropathy and oxidative stress were assessed in these four groups of mice, by biochemical analyses of blood and urine, as well as by histological analyses of the kidneys., Results: Haemoglobin A1c (HbA1c) levels of diabetic TRX1-Tg were not significantly different from those of the diabetic WT. Nevertheless, an augmented urinary albumin excretion observed in diabetic WT was significantly diminished in diabetic TRX1-Tg. Histological study revealed that pathological changes such as mesangial matrix expansion and tubular injury were significantly prevented in diabetic TRX1-Tg accompanied by a reduced tendency of expression of transforming growth factor-beta as compared with diabetic WT. In parallel, urinary excretion of 8-hydroxy-2'-deoxyguanosine and acrolein adduct and the immunostaining intensities of these markers in the kidney were significantly higher in diabetic WT compared with non-diabetic mice. The markers were significantly suppressed in diabetic TRX1-Tg, an indication of systemic and renal oxidative stress attenuation by TRX1 overexpression., Conclusion: These findings indicated the significant role of oxidative stress in the development of diabetic nephropathy and a potential inhibition of progression of nephropathy by TRX1.

Thioredoxin binding protein-2 (TBP-2), which is identical with vitamin D3 (VD3) up-regulated protein 1 (VDUP1), plays a crucial role in the integration of glucose and lipid metabolism. There are three highly homologous genes of TBP-2/vitamin D3 up-regulated protein 1 in humans, but their functions remain unclear. Here we characterized a TBP-2 homolog, TBP-2-like inducible membrane protein (TLIMP). In contrast to TBP-2, TLIMP displayed no significant binding affinity for thioredoxin. TLIMP exhibited an inner membrane-associated pattern of distribution and also colocalized with transferrin and low-density lipoprotein, indicating endosome- and lysosome-associated functions. VD3 and ligands of peroxisome proliferator-activated receptor (PPAR)-gamma, an important regulator of energy metabolism and cell growth inhibition, induced the expression of TLIMP as well as TBP-2. Overexpression of TLIMP suppressed both anchorage-dependent and -independent cell growth and PPARgamma ligand-inducible gene activation. These results suggest that TLIMP, a novel VD3- or PPARgamma ligand-inducible membrane-associated protein, plays a regulatory role in cell proliferation and PPARgamma activation.

Oct-4 is a transcriptional regulator required to maintain the totipotentiality of embryonic stem (ES) cells. Downregulation of its activity is required for proper differentiation of the blastocyst during uterine implantation. Uterine implantation and subsequent vascularization increase oxygen exposure of the developing embryo, thereby altering the intracellular reduction-oxidation status. We tested whether Oct-4 could be regulated by these changes in reduction-oxidation status. We found that Oct-4 DNA binding was exquisitely sensitive to abrogation by oxidation but that the DNA binding of another ES cell transcription factor, FoxD3, was much less sensitive to oxidation. The reducing enzyme Thioredoxin (but not Ape-1) could restore DNA-binding activity of Oct-4. Thioredoxin was less effective at restoring the DNA-binding ability of FoxD3. It was also found that Thioredoxin (but not Ape-1) could physically associate with cysteines in the POU domain of Oct-4. Finally, overexpressing normal Thioredoxin increased the transcriptional activity of Oct-4, while overexpressing a mutant Thioredoxin decreased the transcriptional activity of Oct-4. These data imply that ES cell transcription factors are differentially sensitive to oxidation and that Thioredoxin may differentially regulate ES cell transcription factors.

Uterine leiomyomas are the most common benign smooth muscle tumors in the myometrium. The expression of redox factor 1 (Ref-1), a DNA repair enzyme and redox-modifying factor, was studied in the myometrium and uterine smooth muscle tumors to investigate the relevance of Ref-1 in the growth regulation of the tumors. Two forms of Ref-1 protein were detected, using three antibodies against different epitopes of Ref-1. The abundance of the large form of Ref-1 was increased in leiomyoma extracts relative to myometrial tissue extracts, and the large form was dominant in cell lines derived from leiomyosarcomas. A single mRNA transcript was detected in the same samples, leading us to hypothesize that the differentially migrating forms are the result of posttranslational modification(s). In vitro incubation of leiomyoma tissue extract lead to a shift from the large form to the small form, and this conversion was inhibited by either protease or phosphatase inhibitors. Finally, the relative abundance of the large form of Ref-1 was found to correlate with proliferating cell nuclear antigen levels, suggesting a correlation with increased proliferation. These results indicate that altered posttranslational modification of Ref-1 is involved in uterine smooth muscle tumorigenesis.

Tyrosine phosphorylation of cellular proteins, controlled coordinately by tyrosine kinases and phosphatases, is a critical element in signal transduction pathways involved in the regulation of biological responses including cell growth and differentiation. Decidualization is a dramatic progesterone-induced differentiation of the estrogen-primed endometrium, which is crucial for embryo implantation and maintenance of pregnancy. Here we have shown that the kinase activity of c-Src was increased, accompanied by altered tyrosine phosphorylation of several cellular proteins, during in vitro decidualization of human endometrial stromal cells. Withdrawal of both estrogen and progesterone from the cultures of decidualized stromal cells reduced c-Src kinase activity to the basal level and also changed the pattern of tyrosine phosphorylation of the several cellular proteins to the unstimulated state. The kinase activity of endometrial c-Src appeared to inversely correlate with the level of its tyrosine phosphorylation. Moreover, although the endometrial stromal cells expressed another src-family kinase, Fyn, the activity of the Fyn kinase was almost undetectable during decidualization and thereafter upon steroid withdrawal. Our findings suggest that the activation of c-Src kinase may be a normal physiological event associated with decidualization, being specifically involved in the signaling cascades mediated by ovarian hormone stimulation.

The granulocyte colony-stimulating factor (G-CSF)-induced gene, GIG-1, was originally cloned from G-CSF-stimulated bone marrow mononuclear cells obtained from a patient with chronic myelogenous leukemia (CML). We have characterized the GIG-1 gene and its protein product. Expression of GIG-1 mRNA was elevated by treatment with G-CSF in normal bone marrow mononuclear cells, as well as in some cases of blast cells obtained from patients with acute myelogenous leukemia (AML) and CML. Western blot analysis with anti-GIG-1 peptide antiserum showed the molecular mass of GIG-1 product was about 17 kDa. Immunostaining of the hematopoietic cells demonstrated that GIG-1 product was mainly localized to the cytoplasm of both myeloid and natural killer (NK) cells. These results suggested that GIG-1 protein is an integral component that is accumulated during the differentiation of myeloid cells toward the stage of mature neutrophils. Expression of GIG-1 gene in mature neutrophils was tightly regulated and reactivation of GIG-1 gene by G-CSF in mature neutrophils may represent a compensation process for the protein lost through the activation of these cells, thus implying an important role for this protein in host defense mechanisms.

Human thioredoxin (hTrx) is a cellular redox-active protein that catalyzes dithiol/disulfide exchange reactions, thus controlling multiple biological functions, including cell growth-promoting activity. Here we show that the expression of hTrx protein and messenger RNA was up-regulated by incubation with 17beta-estradiol (E2) in primary culture of stromal cells isolated from human endometrium. Maximal enhancement of hTrx protein and messenger RNA was observed after 6-12 h of incubation with 10-100 nM E2, and the enhancing effect was suppressed by tamoxifen, an estrogen antagonist. Release of hTrx into the culture medium was markedly augmented after 5-day exposure of E2 plus progesterone (P) accompanied by in vitro differentiation of endometrial stromal cells (decidualization). Immunocytochemical studies showed that hTrx was localized in the nucleus, nucleolus, and cytosol in the stromal cells. Strongly enhanced immunoreactivity for hTrx was observed in the E2-treated cells, whereas there was no apparent difference in the pattern of subcellular localization among the untreated and E2- and/or P-treated cells. Although 1-50 microg/ml recombinant hTrx alone did not promote endometrial stromal cell growth, epidermal growth factor-dependent mitogenesis was additively enhanced by hTrx. Our results indicate that hTrx modulates endometrial cell growth, acting as a comitogenic factor for epidermal growth factor, which is known to be a mediator of estrogen action. It is also suggested that hTrx is deeply involved in the hormonal control of the endometrium by E2 and P, playing a regulatory role in endometrial cell growth and differentiation.

Redox regulation of transcription factors has recently been demonstrated for AP-1, NF-kappaB, Sp-1 and glucocorticoid receptor in vitro and in vivo. The redox state in estrogen-dependent cells possibly influences the function of estrogen receptor (ER), and the regulation of the function of ER is essential for understanding of growth and differentiation of these cells, as well as promotion and progression of estrogen-associated cancer. In this paper, we first analyzed the effects of redox state on transcriptional activity of ER in terms of pS2 mRNA expression and transfection of ERE-CAT plasmid in human breast cancer cells. Addition of H2O2 at low concentrations lowered levels of pS2 mRNA and also down-regulated ERE-CAT activity, which was recovered by transfection of thioredoxin (TRX) expression vector. Next, the transfection of antisense TRX plasmid diminished ERE-CAT activity, and the activity was recovered by co-transfected sense TRX. Furthermore, specific DNA binding activity of recombinant ER was inhibited by sulfhydryl-modifying reagents and restored by the addition of recombinant TRX protein in electrophoretic mobility shift assay. These results in vitro and in vivo revealed that the transcription activity of ER is strongly influenced by its redox state, which is reversibly modulated by endogenous redox effector protein, TRX.

Adult T cell leukemia-derived factor (ADF) is a human thioredoxin (Trx) and is a disulfide reducing protein with various biological functions. We found that expression of the ADF/Trx gene was increased by oxidative agents such as hydrogen peroxide, diamide and menadione in Jurkat cells. Analysis using a CAT expression vector plasmid under the control of the ADF/Trx gene promoter revealed that CAT gene expression in Jurkat cells was increased after exposure to oxidative agents. A series of deletion analyses showed that a region from -976 to -890 of the 5' flanking sequence was required for enhancement of ADF/Trx promoter activity against the oxidative agents. Gel mobility shift assay revealed the specific DNA binding activities to the sequences from -953 to -930 in the nuclear extracts from the Jurkat cells. The sequences in this region showed no homology with any known consensus sequences for DNA binding factors. It is suggested that ADF/Trx gene expression is enhanced through a novel cis-acting regulatory element responsive for the oxidative stress and a new factor(s) is involved in this oxidative stress responsive element.

Adult T-cell leukaemia-derived factor (ADF), homologous to thioredoxin, displays various biological activities, such as radical scavenging action and the reduction of protein disulphide bonds. We examined the biochemical and immunohistochemical localization of ADF in the pregnant human uterus, using two heteroantibodies to ADF, antibody C and W. Immunohistochemically, decidua and trophoblast cells were intensely stained by antibody C. The concentration of ADF-like substance in the decidua was 95.9 ng/mg protein, determined by enzyme-linked immunosorbent assay. The molecular weight of ADF-like substance in these tissues was determined by gel electrophoresis to be 13 kDa, the same as that of recombinant ADF. These findings indicate that abundant ADF is present in decidua and trophoblast cells; the localization of such a potent dithiol reducing substance may be beneficial in protecting the fertilized egg and placental trophoblasts from the cytotoxic effects of oxygen radicals.

Serum levels of IL-8 were determined in HIV-infected individuals and the results were compared with those for HIV- controls. The IL-8 levels were measured by an ELISA with a MoAb and a polyclonal antibody to recombinant IL-8. The means and 95% confidence intervals of IL-8 in sera of 36 HIV-infected individuals and 32 matched controls were 275 and 216-349 pg/ml, and 8 and 4-14 pg/ml, respectively, showing a 34-fold increase in IL-8 in the circulation of HIV-infected individuals. This increase does not appear to be related to the disease state, infection or systemic medical agents. This finding suggests the possible involvement of IL-8 in the pathogenesis of HIV-induced disease.

A role for redox regulation in activation of the NF-kappa B transcription factor was suggested by the observation that DNA binding activity of free protein, but not preformed DNA-protein complex, is inhibited by -SH modifying agents but enhanced by reducing agents. Mutagenesis of conserved cysteine residues in the p50 subunit identified amino acid 62 as being important for DNA binding, as a serine substitution at this position reduces DNA binding affinity, but renders the protein insensitive to -SH modifying agents. DNA binding activity of the wild type protein but not the amino acid 62 mutant was also stimulated by thioredoxin while detection of disulphide cross linked dimers in p50 but not the amino acid 62 mutant suggests that thioredoxin stimulates DNA binding by reduction of a disulphide bond involving cysteine 62. The physiological relevance of these findings was supported by the observation that cotransfection of a plasmid expressing human thioredoxin and an HIV LTR driven reporter construct resulted in an NF-kappa B dependent increase in expression of the reporter gene. Thus modification of p50 by thioredoxin, a gene induced by stimulation of T-lymphocytes in parallel with NF-kappa B translocation, is a likely step in the cascade of events leading to full NF-kappa B activation.

The serum levels of soluble IL-2 receptor (sIL-2R), IL-4 and IgE-binding factors were examined in children with allergic diseases, and compared with those in non-allergic controls of the same age and sex. The results showed age-related decreases in the serum levels of sIL-2R and IgE-binding factors, but not in that of IL-4 in both allergic and non-allergic individuals. Significant elevation of sIL-2R was observed in sera from children with atopic eczema or history of an anaphylactic reaction to food, as compared with that in non-allergic controls. The serum concentration of IL-4 was elevated in all allergic groups, including cases of atopic eczema, bronchial asthma and anaphylaxis to food, compared with non-allergic controls, and was correlated significantly with the serum level of IgE (r = 0.59). The IgE-binding factor levels in sera from patients aged 6-10 years with bronchial asthma, or patients aged 1-5 years with a history of food anaphylaxis were elevated as compared with those in non-allergic controls of same age. There was no significant correlation between the serum levels of IgE-binding factors and IgE. Since sIL-2R is released by activated T cells, the present study is in favour of T cell activation causing allergic skin disorders. The serum levels of IL-4 as well as IgE did not differ among allergic patients of different clinical categories. The role of IgE in atopic eczema and other allergic diseases is not clearly established; however, it seems likely that IL-4 is deeply involved in the increased production of IgE seen in allergic individuals. The possible involvement of IgE-binding factors in the age-related changes of clinical manifestations in childhood allergic diseases was also discussed.

Cells expressing Fc receptors for IgE (Fc epsilon RII) were identified in the peripheral blood from patients with atopic dermatitis and with eczematous dermatitis, and normal non-atopic subjects by using monoclonal antibodies to human lymphocyte Fc epsilon RII, and to lymphoid cell-surface antigens by immunofluorescence staining. Based on the extent of the dermatitis patients were classified as severe (greater than 50% skin surface involved), moderate (50-10%) and mild (less than 10%). Patients with severe and moderate atopic dermatitis had 5.9% and 5.7% Fc epsilon RII+ peripheral blood mononuclear cells (PBMC), respectively, that were significantly higher than percentages in mild atopic dermatitis patients (2.6%), severe to moderate eczematous dermatitis patients (2.3%), mild eczematous dermatitis patients (2.2%) and normal individuals (1.7%)(0.05 greater than P). In severe and moderate atopic dermatitis patients, 10% of Fc epsilon RII+ PBMC were T cells that preferentially expressed CD8, and the remainder B cells and monocytes. Fc epsilon RII+ T cells comprised 1% of peripheral T cells, while half or more of peripheral B cells expressed Fc epsilon RII. In mild atopic dermatitis patients, eczematous dermatitis patients and normal subjects. Fc epsilon RII were expressed exclusively on 25-35% of peripheral B cells. Short-term treatment and long-term follow-up of atopic dermatitis patients revealed that changes in the skin condition were related closely to fluctuations in the proportion of Fc epsilon RII+ PBMC. Total serum IgE levels and atopic respiratory allergy did not influence the percentage of Fc epsilon RII+ PBMC. These findings suggest that the percentage of Fc epsilon RII+ PBMC reflects the extent of atopic dermatitis.

The cell surface expression of low-affinity Fc epsilon receptor (Fc epsilon RII), which is identical to CD23, and the serum levels of IgE binding factors (IgE BFs), a soluble form of Fc epsilon RII, and IgE were investigated in HTLV-I-infected individuals, and the results were compared with those for HTLV-I-negative controls. The occurrence of Fc epsilon RII+ mononuclear cells did not differ among the blood samples from the HTLV-I-infected groups; however, the levels of serum IgE BFs were significantly decreased (P less than 0.001) in patients with adult T cell leukaemia (ATL), compared with HTLV-I-negative controls. The serum IgE levels were also significantly decreased in these groups, including cases of ATL (P less than 0.001) and HTLV-I-associated myelopathy (P less than 0.05), and HTLV-I carriers (P less than 0.05), as compared with HTLV-I-negative controls. Since cases of strongyloidiasis or filariasis are frequently found among HTLV-I-infected individuals in Japan, these results may explain in part their defective defence mechanisms for parasites. The possible involvement of IgE BFs in the development of immune deficiency state in HTLV-I infection is also discussed.

We have cloned cDNA encoding the mouse interleukin-2 (IL-2) receptor from a murine T cell line, CTLL using human IL-2 receptor cDNA as probe. COS 7 cells transfected with the cDNA expressed the antigen recognized by the monoclonal antibody against the murine IL-2 receptor. The cDNA identified 4 species of mRNA (4.5, 3.5, 2.2 and 1.5 kb) of the mouse IL-2 receptor in CTLL cells. Difference in the length of mRNA seems to be ascribed to the variable length of the 3' untranslated sequence. Total nucleotide sequence (approximately 1400 bp) of this cDNA was determined and compared with the human receptor. The nucleotide and amino acid sequences of the IL-2 receptor are 70% and 60%, respectively, homologous in average between the two species. The comparison has revealed several conserved regions localized to particular exons such as transmembrane and cytoplasmic portions, suggesting that these regions are important for receptor function and its regulation.

Sera obtained from patients with systemic lupus erythematosus (SLE) were tested for their reactivity to cell lines derived from cutaneous T-cell lymphoma (CTCL), or adult T cell leukaemia (ATL), and with other cell lines, by indirect immunofluorescence method. Approximately one half of SLE sera reacted with the surface antigens of HUT-102 cells, a cell line from CTCL, which constitutively expresses Tac antigen. The titre tended to be higher in the active than in the inactive stage. These positive sera also reacted with other neoplastic or normal T cell lines having Tac antigen. SLE sera reacting with HUT-102 surface antigens were further examined for their reactivities to Tac antigen, the putative IL-2 receptor, using HUT-102 or ATL-2. Pretreatment with anti-Tac monoclonal antibody partially blocked the reactivities to HUT-102 surface antigens in nine of 15 SLE sera tested. The binding of 125I-labelled anti-Tac monoclonal antibody was displaced by the addition of sera from six of 15 SLE patients. In addition, nine of the 15 SLE sera could inhibit the binding of 125I-labelled IL-2 to ATL-2 cells. These results suggested that some of SLE sera contained antibodies against the IL-2 receptor.

Very recently, it has been reported that interleukin-1 (IL-1) has an inhibitory effect on progesterone production by porcine granulosa cells in vitro. In the present study we investigated the presence of IL-1 or IL-1-like activity in porcine ovarian follicular fluids (FF) as the first step in elucidating the physiological role of IL-1 in follicular growth and maturation. Since IL-1 and IL-1-like substances have interleukin-2 receptor (IL-2R)/p55(Tac)-inducing activity (TIA), we determined the TIA in the FF by means of a highly sensitive TIA assay using flow cytometry. TIA was significantly higher (P less than 0.01) in the FF of small follicles than in those of medium-sized and large follicles. A significant negative correlation (P less than 0.05) was apparent between TIA and 17 beta-estradiol concentration in the FF. The conditioned media of porcine granulosa cells also showed TIA. Of these conditioned media, those from small follicles exhibited higher TIA than those from medium-sized and large follicles. TIA in the conditioned media decreased rapidly as the culture period was extended. Sex steroids such as 17 beta-estradiol, progesterone, testosterone, and androstenedione had no effect on IL-2R/p55(Tac) induction. These results indicate that porcine granulosa cells produce the IL-2R/p55(Tac)-inducing factor, the activity of which decreases in association with the maturation of the follicles. Because of the heterogeneity of IL-2R-inducing factors, the relationship between TIA in the FF and IL-1 should be elucidated. We discuss the possibility that this factor may play a role in follicular maturation and that enhancement of IL-2R/p55(Tac) expression by this factor may contribute to the local defense mechanism in ovarian follicles.

Fc epsilon receptor (Fc epsilon R) expression on several human cell lines (U937, RPMI 8866, HL 60, THP-1, and Molt 4) and its regulation were examined by immunofluorescent analysis using a monoclonal anti-human Fc epsilon R antibody, H107. Phorbol ester (PMA), recombinant gamma interferon (IFN-gamma) and H107 itself enhanced Fc epsilon R expression on a FC epsilon R positive cell line U937, whereas these reagents did not induce FC epsilon R expression on the Fc epsilon R negative cell lines, Molt 4, HL 60 and THP-1. Dexamethasone not only suppressed by 50% the spontaneous Fc epsilon R expression on U937 cells but also completely inhibited the enhancement of their Fc epsilon R expression on U937 cells induced by PMA, IFN-gamma or H107. Dexamethasone caused a little suppression of Fc epsilon R expression by RPMI 8866 cells. The results showed that Fc epsilon R expression on a human monoblast cell line U937 was up- or down-regulated by a variety of physiological or pharmacological agents. These experimental systems provide a good model for the investigation of the regulatory mechanisms of Fc epsilon R expression.