https://zenodo.org/record/1260015/files/article.pdf

Toxoplasmosis of rats: a review, with considerations of their value as an animal model and their possible role in epidemiology.

Prolactin (PRL) was originally identified as a neuroendocrine hormone of pituitary origin (Riddle & Braucher 1931, Riddle et al. 1933). While the primary function of this hormone was initially thought to lie solely within the breast, the functional pleiotropism of this peptide with regards to reproduction, osmoregulation, and behavior was subsequently recognized (Nicoll 1974). Several lines of evidence have now also demonstrated an immunoregulatory role for this peptide. Structural analysis of PRL has revealed it to be related to members of the cytokine/ hematopoietin family such as growth hormone (GH), erythropoietin, granulocyte–macrophage colony stimulating factor (GM-CSF) and the interleukins (IL) IL-2 to IL-7 (Bazan 1990). Synthesis of PRL is not limited to the hypophysis, as numerous extra-pituitary sites of PRL expression including the decidua, breast, and T lymphocytes have been detected (DiMattia et al. 1986, Montogomery et al. 1987, Clevenger et al. 1990, Gellersen et al. 1994, Ginsburg & Vonderhaar 1995, Mershon et al. 1995, Clevenger & Plank 1997). The receptor for PRL (PRLr) is present on T and B lymphocytes and macrophages (Pellegrini et al. 1992, Dardenne et al. 1994). Acting through its receptor, PRL modulates immune system function by stimulating both cell proliferation and survival. Taken together, these data indicate that PRL acts at the endocrine, paracrine, and autocrine levels in regulating immune function (Gala 1991, Prystowsky & Clevenger 1994, Kooijman et al. 1996, Yu-Lee 1997). This review initially focuses on the immunoregulatory functions of PRL in the immune system, and then focuses on the structure/ function relationships within the PRLr as they pertain to immunologically relevant signal transduction pathways.

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Prolactin receptor signal transduction in cells of the immune system.

A review of current literature on mammalian hosts' sexual dimorphism (SD) in parasitic infections revealed that (1) it is a scarcely and superficially studied biological phenomenon of considerable significance for individual health, behavior, and lifestyles and for the evolution of species; (2) there are many notable exceptions to the rule of a favorable female bias in susceptibility to infection; (3) a complex network of molecular and cellular reactions connecting the host's immuno-neuroendocrine systems with those of the parasite is responsible for the host-parasite relationship rather than just an adaptive immune response and sex hormones; (4) a lack of gender-specific immune profiles in response to different infections; (5) the direct effects of the host hormones on parasite physiology may significantly contribute to SD in parasitism; and (6) the need to enrich the reductionist approach to complex biological issues, like SD, with more penetrating approaches to the study of cause-effect relationships, i.e., network theory. The review concludes by advising against generalization regarding SD and parasitism and by pointing to some of the most promising lines of research.

Host gender in parasitic infections of mammals: an evaluation of the female host supremacy paradigm

The expression and function of the newly identified Bcl-2- and Raf-1- binding protein, Bag-1, during the cytokine-regulated growth of B and T cell lines was examined. Immunoblot analysis of lysates from the interleukin-3 (IL-3)-dependent B cell line Ba/F3, and the PRL-dependent T cell line Nb2, revealed that variations in Bag-1 levels paralleled alterations in cellular proliferation, viability, and apoptosis induced by the presence or absence of growth factor. To test whether up-regulation of Bag-1 levels altered cellular survival and proliferation, Ba/F3 cells were transfected with a Bag-1 expression construct. The overexpression of Bag-1 in transfected Ba/F3 cells induced an IL-3-independent state. Such transfectants demonstrated sustained viability and proliferation, with minimal apoptosis, in the complete absence of exogenous IL-3. Bag-1 expression was also compared in glucocorticoid-sensitive Nb2 cells and a PRL-independent, glucocorticoid-resistant subline, SFJCD1, during culture of these lines in d...

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Role of Bag-1 in the Survival and Proliferation of the Cytokine-Dependent Lymphocyte Lines, Ba/F3 and Nb2

We have examined the neuroimmunoregulatory function of prolactin (PRL) on astrocytic inducible nitric oxide synthase (iNOS) expression in the C6 glioma cell line. After 24 h of PRL (5-100 nM) stimulation, a concentration-dependent increase of NO release, evaluated as nitrite, was observed in C6 culture medium. Moreover, both NO release and iNOS expression induced by interferon-gamma (250 U/ml) were enhanced by PRL (18-100 nM). PRL-induced NO release was inhibited by dexamethasone, an inhibitor of de novo iNOS synthesis. We used erbstatin (5 microg/ml), a potent inhibitor of protein tyrosine kinases, to test whether these proteins were required for signaling events evoked by PRL in these cells. This inhibitor was able to inhibit completely the PRL-induced NO production and iNOS expression. In conclusion, we provide evidence that NO production in glial cells can be regulated not only by cytokines but also by neuroimmunoregulatory hormones such as PRL, which is present in normal brain but may be elevated in several pathological states.

Prolactin Induction of Nitric Oxide Synthase in Rat C6 Glioma Cells

Effect of prolactin, rIFN-gamma or rTNF-alpha in murine toxoplasmosis.

Effects of alpha-adrenergic agonists on Toxoplasma gondii replication in human umbilical vein endothelial cells.

Rats are resistant to Toxoplasma infection, and in contrast to mice do not form cysts in their tissues. Because rats treated with beta adrenergics, corticosteroids or 60cobalt are more susceptible to toxoplasmosis, we conducted experiments to investigate if the impaired resistance of drug-treated rats is related to macrophage function or induction of cystogenic capacity. Our experiments in 0.7 or 1.2 mg/kg-corticosteroid or 12 Gy-60cobalt-treated rats indicated that the decreased survival rate (P < 0.001 to P < 0.0001, compared to infected-untreated or infected-unirradiated animals) was associated with a decrease of both macrophage toxoplasmastatic activity and intracellular killing (P < 0.05 each group), compared to infected-untreated or infected-unirradiated rats. However in 9 Gy-60cobalt-treated animals the decreased survival rate (P < 0.001, compared with control rats) was accompanied only by a decrease of the toxoplasmastatic activity in comparison to macrophages of the control animals. Moreover in these animals, the release of NO2- by these macrophages was poorly detectable (P < 0.05) or completely inhibited (P < 0.01) in comparison with infected-untreated or infected-unirradiated rats. In contrast, in all groups of rats treated with high doses of beta adrenergic, the decreased survival (P < 0.001 to P < 0.0001, compared with untreated rats) was accompanied by values of intracellular killing and intracellular proliferation of Toxoplasma parasites that did not significantly (P = ns each group) differ from macrophages of infected-untreated rats. Furthermore in the high beta adrenergic treated groups only small amounts of NO2- were detectable (P < 0.05) in comparison with control animals. In addition, our data in rats treated with 0.7 or 1.2 mg/kg of corticosteroid or 12 Gy of 60cobalt indicated that the increased mortality was correlated to the presence of a small number of cysts in their brains (P < 0.05; P = ns; P < 0.01 respectively) in comparison to infected-untreated or infected-unirradiated rats. These results suggest that the susceptibility of drug-immunosuppressed rats is not due exclusively to a deficient macrophage function, but is probably also linked to immune mechanisms involved in the process of cystogenesis.

Susceptibility to toxoplasmosis: correlation between macrophage function, brain cyst formation and mortality in rats.

Cytokine-activated human vein endothelial cells (HUVEC) may play an important role in resistance to Toxoplasma gondii infection. In this study, it was investigated the role of rTNF-alpha and GH in the induction of antitoxoplasmal activities in HUVEC. Co-treatment of HUVEC with rTNF-alpha plus GH induced both toxoplasmastatic activity and the intracellular killing of T. gondii (p <0.01 each vs untreated cells). Thus, these functions were inhibited by both neutralizing antibodies to IL-6 and GM-CSF (but not to IL-3) suggesting that these cytokines participate in the inhibitory process. Consistent with this hypothesis, the treatment of HUVEC with rIL-6 or rGM-CSF in the presence of rTNF-alpha, limited T. gondii multiplication in a dose-dependent manner (p <0.01 each vs untreated cells). In order to elucidate the inhibitory mechanism of HUVEC, it was assessed by L-arginine analogs (e.g., NG-monomethyl-arginine) whether NO2 molecules originating from HUVEC were directly or indirectly involved in the rTNF-alpha/GH-dependent induction of toxoplasmastatic activity. A good correlation was found between toxoplasmastatic activity and NO2 release during the activation phase, before infection of the HUVEC with T. gondii, but no correlation was found between the parasitostatic activity and NO2 release during the infection phase. These data indicate that NO2- itself does not directly affect toxoplasmastatic activity. Besides, the reduction of intracellular killing by monoclonal antibodies to ICAM-1 suggest that this adhesin plays a role in controlling T. gondii entry into cells.

Interactions between cytokines and growth hormone for resistance to experimental.

Impairment of natural resistance to Toxoplasma gondii infection in rats treated with beta adrenergics, beta blockers, corticosteroids or total body irradiation.

Folgore A

Papers

Effect of prolactin, rIFN-gamma or rTNF-alpha in murine toxoplasmosis.

Effects of alpha-adrenergic agonists on Toxoplasma gondii replication in human umbilical vein endothelial cells.

Susceptibility to toxoplasmosis: correlation between macrophage function, brain cyst formation and mortality in rats.

Interactions between cytokines and growth hormone for resistance to experimental.

Impairment of natural resistance to Toxoplasma gondii infection in rats treated with beta adrenergics, beta blockers, corticosteroids or total body irradiation.