PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Thymic Factor, Circulating”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1985

Effect of thymulin on intracellular cyclic nucleotides and prostaglandins E2 in peanut agglutinin-fractionated thymocytes.

Prostaglandin E2 (PGE2) and other selected agents which elevate intracellular cyclic AMP (cAMP) levels have been demonstrated to induce the appearance of surface markers in immature T lymphocytes. Thymic hormones, which are the natural inducers of these markers, have long been hypothesized to act through the increase of cAMP levels. We have approached this area of investigation by studying the effects of thymulin (a serum thymus-derived factor, coupled with Zinc) on intracellular cAMP and cyclic GMP (cGMP) levels (expressed as cAMP/cGMP ratio) and on the release of PGE2 in different thymocyte subpopulations. Thymocytes were fractionated by the peanut agglutinin (PNA) technique into cortical immature PNA+ and medullary mature PNA- thymocytes. The data presented in this report show that thymulin is able to increase the cAMP/cGMP ratio in PNA+ and in unfractionated thymocytes, depending on its concentration, but not in PNA- thymic cells. Conversely, it is able to increase the release of PGE2 by PNA- thymocytes but not by PNA+ and unfractionated thymic lymphocytes. These results are consistent with the hypothesis that thymulin could act through different mechanisms depending on the differentiation stage of its target cells. In fact, it could be suggested that immature T cells could be activated by thymulin thereby increasing the cAMP/cGMP ratio, whereas more mature T cells would be further differentiated by thymulin through enhanced release of PGE2.

Animals↗
PubMed1987

Stimulatory effects of cyclosporin A on human and mouse thymic epithelial cells.

When injected daily into normal young or aging mice, cyclosporin A (CsA) induces a significant stimulation of thymic hormone (thymulin) secretion, as measured by the peripheral level of the hormone and the number of thymulin-producing cells in the thymus. This stimulation is dose dependent and reversible after the end of treatment. Similar findings have been made in primary cultures of human thymic epithelial cells in which CsA increases the percentage of thymulin-producing cells evaluated by immunofluorescence, as well as the amount of hormone released into the supernatants. No effect of CsA is observed on the expression of class II major histocompatibility complex antigens. CsA also increases the proliferation of cultured human thymic epithelial cells, as assessed by bromodeoxyuridine and [3H]thymidine incorporation. The present study strongly suggests that CsA can stimulate the proliferation and endocrine function of thymic epithelial cells. Its action on the immune system is thus not restricted to lymphoid cells and might be partially mediated by its effect on the thymic epithelium.

Animals↗
PubMed1995

Functional gap junctions in thymic epithelial cells are formed by connexin 43.

A multiparametric study was carried out to investigate the presence and possible role of communicating junctions in the thymus, particularly in the thymic epithelium, the major component of the thymic microenvironment. The presence of direct cell-cell communication mediated by gap junctions was demonstrated in human and murine thymic epithelial cells (TEC) by means of in situ and in vitro immunohistochemical labeling as well as in vitro fluorochrome injection and double whole-cell patch clamp experiments. Moreover, both immuno- and Northern blot studies revealed that the gap junction protein connexin 43 and its mRNA were present in TEC. Importantly, we showed that thymic endocrine activity, as ascertained by thymulin production, could be specifically down-modulated in vitro by a gap junction inhibitor, octanol. We also investigated the existence of gap junctions between TEC and thymocytes. In thymic nurse cells we were able to detect cell-cell communication, although only a minor percentage of epithelial/thymocyte pairs were coupled in a given moment. In contrast, intercellular communication was not detected between cultured phagocytic cells of the thymic reticulum and the respective rosetting thymocytes. We suggest that gap junctions formed by connexin 43 may represent a novel (and rather cell type-specific) pathway for intrathymic cellular communication, including TEC/TEC as well as possible TEC/thymocyte interactions.

Animals↗
PubMed1981

Influence of serum thymic factor (FTS) on radiation-induced leukaemogenesis in thymectomized AKR mice.

The influence of serum thymic factor (FTS) on extrathymic leukaemogenesis induced in thymectomized AKR mice by fractionated sub-lethal irradiation was studied. Thirty-day-old thymectomized mice were submitted to four doses at weekly intervals (1.75 Gy) and thereafter treated with FTS (1 ng) for 9 days. Two groups were restored with either bone marrow or spleen cells prior to FTS treatment. In another group mice were treated with FTS (12 ng) for 1 month after thymectomy and prior to irradiation. Results indicated that primarily irradiation and FTS, and, to a lesser extent, restoration and age of the mice at the time of their first radiation exposure influenced leukaemogenesis. Irradiation increased the spontaneous low incidence of extrathymic leukaemia (5%) up to 50%. Although nothing is yet known about the expression of endogenous retroviruses in thymectomized AKR mice, the possible expression of leukaemogenic recombinants, either identical to or different from mink-cell-focus-inducing viruses (MCF), might explain this enhancing effect of radiation on leukaemogenesis. Mice developed two types of leukaemias: "null" leukaemias whose cells bore no detectable theta antigen or surface immunoglobulin, and B leukaemias. Among the null leukaemias, two kinds could be distinguished: "early" ones which were observed before 450 days, and in which BM and spleen were similarly involved, and "late" ones which displayed the same characteristics as B leukaemias, i.e. delayed appearance (after 450 days) and splenic origin. Although FTS did not modify the overall frequency of leukaemias, it increased significantly the incidence of the "early" null ones. It had no effect on the frequency or the latency of late null and B leukaemias. Any population of theta-negative T cells sensitive to FTS could be an acceptable candidate for "early" null leukaemogenesis. The origin of "late" null leukaemias remains an open question.

Age Factors↗
PubMed1992

Establishment of a sensitive radioimmunoassay for serum thymic factor with a special reference to extraction procedures.

A radioimmunoassay (RIA) for serum thymic factor (facteur thymique serique) was established. This assay could detect less than 0.5 pg of serum thymic factor without the interference by other thymic hormones, including thymopoietin II and thymosin alpha 1. Both zinc-free and zinc-bound serum thymic factor showed a similar standard curve, indicating that this RIA could detect both forms of serum thymic factor in the same way. We observed that two procedures were required prior to the measurement in order to measure serum thymic factor content in plasmas; the first, the extraction procedure to remove substances interfering with the assay nonspecifically; the second, the storage of the sample with ethylenediamine tetraacetic acid disodium salt to inhibit the proteases in the plasma to degrade serum thymic factor. By employing this assay system, we observed that cord blood plasmas contained significantly higher level of serum thymic factor than did adult blood plasmas.

Adult↗
PubMed1980

Effects of thymic factors on growth of experimental tumors.

The effects of thymic factors on the growth of a chemically induced tumor have been studied. The thymic factors were obtained by a gentle isolation procedure which minimizes loss of material and biological activity. The administration of the thymic factors neither influenced the development or growth of the tumor nor the weight of the thymus or the spleen. A bigger thymus and a smaller spleen were observed in animals rejecting the tumor, whether or not they received the thymic factors.

Animals↗
PubMed2000

Immunomodulatory potential of thymulin-Zn(2+) in the alveolar epithelium: amelioration of endotoxin-induced cytokine release and partial amplification of a cytoprotective IL-10-sensitive pathway.

The immunomodulatory potential of thymulin in the perinatal epithelium is not well characterized. In an in vitro model of fetal alveolar type II epithelial cells, we investigated the exhibition of an anti-inflammatory activity of this peptide hormone. Thymulin selectively ameliorated, in a dose-dependent manner, the endotoxin-induced release of IL-1 beta (IC(50) = 657 ng. ml(-1)), but showed no inhibitory effect on IL-6 and TNF-alpha. Zinc, an anti-inflammatory antioxidant, which is required for the biological activity of thymulin, reduced the secretion of IL-1 beta (IC(50) = 62 microM), TNF-alpha (IC(50) = 1000 microM), and, to a lesser extent, IL-6. This cation (100 microM) amplified the effect of thymulin on IL-1 beta and TNF-alpha (IC(50) < 0.1 ng. ml(-1)), but not on IL-6. Analysis of whether thymulin is up-regulating a counterpart anti-inflammatory signaling loop revealed the involvement of an IL-10-sensitive pathway. These results indicate that thymulin acts as a novel dual immunoregulator by enhancing an anti-inflammatory cytoprotective response and depressing an inflammatory signal, an effect synergistically amplified, in part, by cationic zinc.

Adjuvants, Immunologic↗
PubMed2001

Identification of serum factor inducing ectodomain shedding of proHB-EGF and sStudies of noncleavable mutants of proHB-EGF.

The ectodomain of the transmembrane form of HB-EGF (proHB-EGF) is cleaved at the cell surface by proteases, yielding a soluble growth factor. A number of stimuli, including TPA, accelerate this cleavage. However, proHB-EGF is shed constitutively under normal culture conditions without any particular stimuli. We demonstrate here that constitutive cleavage resulted largely from factor(s) contained in supplemented FCS in a culture medium. Analysis of serum factors, including digestion with enzymes, separation by thin layer chromatography, and shedding assay with purified phospholipids, revealed that lysophosphatidic acid (LPA) is a major factor in FCS for stimulation of proHB-EGF shedding. We also studied here ectodomain shedding of two kinds of mutant form of proHB-EGF which have a single amino acid substitution around the putative cleavage sites. These mutant forms showed resistance to stimuli of both TPA and LPA, suggesting that proHB-EGF is cleaved at the similar site by stimulation with TPA and LPA.

Animals↗
PubMed1997

Involvement of interleukin-1 beta, nerve growth factor, and prostaglandin-E2 in the hyperalgesia induced by intraplantar injections of low doses of thymulin.

The effect of various doses of intraplantar thymulin injection, on nociceptive thresholds, in the hind paw of rats was assessed using different pain tests. As little as 0.5 ng thymulin resulted in localized mechanical hyperalgesia as assessed by the paw pressure test and thermal hyperalgesia as assessed by the paw immersion, hot plate, and tail flick tests. The highest dose of thymulin (10 ng) reduced both paw pressure and paw immersion latencies in the noninjected paw also. Thymulin (5 ng) also resulted in significant elevation in the levels of interleukin-1 beta (IL-1 beta) and nerve growth factor (NGF) levels in the injected paw. Both dexamethasone and indomethacin reversed thymulin-induced hyperalgesia. Also interleukin-1 receptor antagonist (IL-1ra) and a polyclonal anti-NGF antiserum significantly reduced thymulin-induced hyperalgesia. On the other hand, the tripeptide lys-D-pro-val (known to antagonize IL-1 beta and PGE2 induced hyperalgesia) reversed the hyperalgesia due to thymulin. In conclusion, thymulin induces localized hyperalgesia which is mediated by PGE2-dependent mechanisms and this pathway could be either partially dependent on or totally independent of IL-1 beta mechanisms.

Animals↗
PubMed2002

Thymulin reduces the hyperalgesia and cytokine upregulation induced by cutaneous leishmaniasis in mice.

Cutaneous leishmaniasis (CL) in mice has been shown to produce hyperalgesia and upregulation of interleukin (IL)-1beta and nerve growth factor (NGF) levels. The aim of this study was to investigate the effects of thymulin on CL-induced hyperalgesia and cytokine upregulation. Daily treatment with thymulin (1, 100, and 1000 ng/ip) produced dose-dependent decreases in CL-induced hyperalgesia as assessed by the tail flick and the hot plate tests. The levels of NGF and IL-1beta were determined in the skin tissues of the hind leg in different groups (n = 5 each) of mice over a period of 5 weeks. Mice with CL showed sustained increase in the levels of IL-1beta and NGF which were reversed by thymulin (1 microg). Injection of thymulin only did not alter the nociceptive thresholds or the levels of IL-1beta and NGF. We conclude that thymulin can modulate the hyperalgesia induced by CL by decreasing the levels of the proinflammatory factors IL-1beta and NGF.

Animals↗
PubMed1996

Effects of a nonapeptide thymic hormone on intestinal intraepithelial lymphocytes in mice following administration of 5-fluorouracil.

A significant fraction of murine small intestinal intraepithelial lymphocytes (i-IELs) mature in local sites outside the thymus. However, there is evidence suggesting that extrathymic differentiation of i-IELs is still influenced by the thymus or thymus-derived factors. Facteur thymique serique (FTS), a nonapeptide thymic hormone, is involved in several aspects of intra- and extrathymic T cell differentiation in vivo. In this study, we investigated the effects of FTS on the kinetics of i-IELs in mice following a single administration of 5-fluorouracil (5-FU). FTS treatment significantly accelerated the recovery in cell number of i-IELs after administration of 5-FU. Flow cytometric analysis revealed that this accelerated recovery was mainly due to a rapid increase in CD8 alpha alpha+ i-IELs. Similar findings were also evident in adult thymectomized (ATX) mice, indicating that FTS treatment caused a rapid recovery of CD8 alpha alpha+ i-IELs following 5-FU administration in the absence of a functional thymus. Furthermore, expression levels of the mRNAs for interleukin-2, interferon-gamma, and transforming growth factor beta 1 in the i-IELs were augmented by FTS treatment. Notably, FTS treatment protected mice from 5-FU-induced lethal toxicity, accompanied with an inhibition of the translocation of Enterobacteriaceae. These results suggest that FTS has an important function in the extrathymic maturation and activation of i-IELs in the small intestine following 5-FU administration, which may contribute at least partly to the protection against 5-FU-induced lethal toxicity.

Animals↗
PubMed1993

Restoration of the thymus in aging mice by in vivo zinc supplementation.

A multiparametric study of the thymus was performed in normal aging mice (12-15 months old) submitted to a mild oral zinc supplementation during 3-6 months as compared to age-matched control mice. First, this study demonstrated that in rodents, zinc levels are significantly reduced with aging and can be restored to values close to those observed in young animals after 6 months of zinc supplementation. Second, our data showed that oral zinc administration stimulates thymus growth and partially restores the microenvironmental as well as lymphoid compartments of the organ. Regarding thymic endocrine function, a significant increase in thymulin levels and a concomitant decrease in plasma thymulin inhibitors were observed, suggesting that the age-related decline of thymic function might at least partially be due to extrinsic factors, such as zinc deficiency. The total number of thymic lymphocytes was consistently increased, without significant changes in CD4/CD8 defined thymocyte subsets. Finally, structural changes of the thymus epithelium were also detected, including the disappearance of epithelial cysts frequently observed in old animals, reappearance of a normal pattern of the thymic epithelial cell network, and a decrease in the extracellular matrix network. Taken together, these data suggest that aging-related physiological zinc deficiency induces some relevant changes in thymus structure and function which can be partially corrected by a mild oral zinc supplementation.

Administration, Oral↗
PubMed1980

One or several thymic hormones?

Four main thymic preparations have been reported in the literature: thymosin, thymopoietin, thymic humoral factor (THF), and serum thymic factor (FTS). Their possible relationships are discussed with reference to their chemical characteristics and their main biologic features.

Animals↗
PubMed1987

Pattern of secretion in thymic epithelial cells: ultrastructural studies of the effect of blockage at various levels.

The observation of secretory phenomena in mouse thymic epithelial cells is disappointing since no real secretion image is found. An adequate technique for such a study is to block the secretion pathway and to observe by electron microscopy cells accumulating secretory products. For this purpose, we used three means of blocking secretion: Firstly, since the thymic epithelial cell is regulated by a feedback phenomenon, secretion was blocked by antibodies against thymulin, one of the hormones secreted by these cells. Secondly, colchicine was used to modify the intracellular transport of the secretory product. In both of these types of experiments, electron microscopy showed a great increase in the number of "clear vacuoles" and their granular contents in epithelial cells. In a third series of experiments, we used monensin at a concentration that blocks the intracellular transport of secretory proteins at the various levels of the Golgi apparatus. In this series, only an increased number of vacuoles was observed, but they appeared devoid of all granular content. It can be concluded that in the thymic epithelial cell, a discrete system of secretion directs the passage of the product, originating in the cisternae of the endoplasmic reticulum, into "clear vacuoles", the terminal element of the cellular secretory apparatus.

Animals↗