Influence of Interferon-γ on Salmonella Typhi Induced Macrophage Apoptosis

Introduction: Salmonella Typhi (S.Typhi), which causes typhoid fever, is a widespread pathogen in developing countries. Interferon-gamma (IFN-γ) is a critical cytokine in host defense against Salmonella infection. IFN-γ provides protection against Salmonella infection by inducing macrophage activation. This study was designed to determine the effect of recombinant IFN-γ (rIFN-γ) on S.Typhi induced macrophage apoptosis and to examine the effect of rIFN-g on caspase-1 expression during apoptosis. Materials and Methods: After isolation of macrophages, apoptotic cells were analyzed using both annexin V-FITC detection kit by fl ow cytometry and TUNEL technique. Caspase-1 expression was determined by RT-PCR. Results: The rIFN-γ concentrations of 100 IU/ml ve 1000 IU/ml decreased macrophage apoptosis caused by S.Typhi, 13.1 % and 6.3 % respectively. Conclusion: Consequently, we observed that rIFN-g decreased Salmonella-induced apoptosis and inhibited caspase-1 expression during apoptosis. It is considered that the modulatory effect of IFN-γ on macrophage apoptosis may impact a protective effect during Salmonella infection and this may help to abort invasive S.Typhi infections

Catechol-O-Methyltransferase Expression and 2-Methoxyestradiol Affect Microtubule Dynamics and Modify Steroid Receptor Signaling in Leiomyoma Cells

CONTEXT: Development of optimal medicinal treatments of uterine leiomyomas represents a significant challenge. 2-Methoxyestradiol (2ME) is an endogenous estrogen metabolite formed by sequential action of CYP450s and catechol-O-methyltransferase (COMT). Our previous study demonstrated that 2ME is a potent antiproliferative, proapoptotic, antiangiogenic, and collagen synthesis inhibitor in human leiomyomas cells (huLM). OBJECTIVES: Our objectives were to investigate whether COMT expression, by the virtue of 2ME formation, affects the growth of huLM, and to explore the cellular and molecular mechanisms whereby COMT expression or treatment with 2ME affect these cells. RESULTS: Our data demonstrated that E(2)-induced proliferation was less pronounced in cells over-expressing COMT or treated with 2ME (500 nM). This effect on cell proliferation was associated with microtubules stabilization and diminution of estrogen receptor alpha (ERalpha) and progesterone receptor (PR) transcriptional activities, due to shifts in their subcellular localization and sequestration in the cytoplasm. In addition, COMT over expression or treatment with 2ME reduced the expression of hypoxia-inducible factor -1alpha (HIF-1 alpha) and the basal level as well as TNF-alpha-induced aromatase (CYP19) expression. CONCLUSIONS: COMT over expression or treatment with 2ME stabilize microtubules, ameliorates E(2)-induced proliferation, inhibits ERalpha and PR signaling, and reduces HIF-1 alpha and CYP19 expression in human uterine leiomyoma cells. Thus, microtubules are a candidate target for treatment of uterine leiomyomas. In addition, the naturally occurring microtubule-targeting agent 2ME represents a potential new therapeutic for uterine leiomyomas

Specifically Cytotoxic Human and Mouse Lymphood Cells Induced with Antibody or Antigen-Antibody Complexes

Abstract Human or mouse lymphoid cells could be “armed” with anti-NIP antibodies to become cytotoxic to NNP-conjugated fowl erythrocytes (NNP and NIP are closely related haptens). The arming factor was neutralized by a sufficient concentration of NIP-BSA (twice the concentration causing maximal precipitation) but low concentrations (e.g., 7% of the maximal precipitation concentration) increased the arming capacity.</jats:p

Two Types of Antibody Dependent Cell-Mediated Cytotoxicity, Arming and Sensitization

Abstract Haptenated chicken erythrocytes, anti-hapten antibodies and normal spleen cells were used for a study of parameters of antibody-dependent cell-mediated cytotoxicity (ADCC). Anti-hapten antibody was introduced to the reaction either bound to the target cells (sensitization) or to the effector cells (arming). Our data suggest that the same effector cells and the same antibodies were responsible for both types of reactions. More antibody was required for arming (ca. 1 ng/ml) than for sensitization (ca. 10 pg/ml). Antibodies of several mammalian species could cooperate in ADCC with human, rat, or guinea pig spleen effector cells, but fowl antibodies were inefficient in the arming of mammalian effector cells. Rat and human spleen cells were powerful effector cells whereas guinea pig, rabbit, and mouse spleens yielded weakly cytotoxic suspensions. Rabbit antibodies, on the other hand, were efficient, but rat antibodies were less efficient in ADCC. Mouse and guinea pig antibodies appear to take an intermediate position. Our data suggest that ADCC effector cells of the spleen contain phagocytic and nonphagocytic cells, and the non-phagocytic effector cells still constitute a heterogeneous population.</jats:p

Effects of some antigenic fractions of Leishmania major on nitric oxide production and IL-12 secretion by murine peritoneal macrophages

Nitric oxide (NO) and IL-12 are important mediators of the immune response to Leishmania major. In this study, the effects of L. major promastigotes, crude antigenic fraction (CAF) and its subfractions on NO production and IL-12 secretion by BALB/c mice peritoneal macrophages is investigated. The subfractions of CAF, namely, fractions 1, 2 and 3, that were in the molecular weight range of 97.4-66, 66-45 and below 45 kDa, respectively, were separated by SDS-PAGE. NO production was determined by using Griess reagent and IL-12 was measured by ELISA. It was found that NO production was stimulated by promastigotes but not by CAF or its subfractions. IL-12 secretion was stimulated by promastigotes, CAF and fraction 1 while fractions 2 and 3 did not have any effect. (C) 1998 Elsevier Science B.V. All rights reserved