Estrogen regulates cytokine production and apoptosis in PMA-differentiated, macrophage-like U937 cells

We have investigated the effects of sex steroids, estradiol (E2), and testosterone (T) on the synthesis of tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) in phorbol-myristate-acetate (PMA)-differentiated human monoblastic U937 cells. The ability of both hormones to modulate the viability and programmed cell death of macrophage-like PMA-differentiated U937 cells was also inspected. E2 increased TNF-alpha synthesis, whereas T had no effect on the production of this cytokine. The combination of E2 and its antagonist tamoxifen or ICI-182,789 completely abolished the induction of TNF-alpha, while combination of T and its antagonist Casodex (CSDX) did not significantly affect …

Modulation of Nitric Oxide Production by Tetracyclines and Chemically Modified Tetracyclines

Chemically modified tetracyclines (CMTs) dose-dependently decreased inducible nitric oxide synthase (iNOS) and, consequently, nitric oxide (NO) formation by the lipopolysaccharide (LPS)-stimulated J774 line. The inhibitory effect was due to a specific reduction in the iNOS protein content in the cells, as attested by Western blot analysis and by the inhibition of iNOS mRNA accumulation. Furthermore, CMTs cause a dose-dependent increase in cell death in the J774 line mediated by the NO-independent apoptotic mechanism.

Cytokines and growth factors in wound drainage fluid from patients undergoing incisional hernia repair

Knowing the dynamics of growth factor and cytokine secretion within the site of a surgical operation is important, as they play a crucial role in the pathophysiology of wound healing and are a target for modifying the repair response. The aim of this study was to evaluate the production of several cytokines and growth factors in the drainage wound fluid from patients undergoing incisional hernia repair: namely, interleukin (IL)-6, IL-10, IL-1alpha, IL-1 ra, interferon-gamma, vascular endothelial growth factors and basic fibroblast growth factor. Ten female patients with abdominal midline incisional hernia undergoing surgical repair were included in this study. In all cases, a closed-suction…

CD4+ / CCR5+ and CD4+ / CCR3+ lymphocyte subset and monocyte apoptosis in patients with acute visceral leishmaniasis

The Acute Phase Response in Sicilian Patients with Boutonneuse Fever Admitted to Hospitals in Palermo, 1992–1997

Abstract Objectives : To study the modifications of some components of the acute phase response (APR) in Sicilian patients with boutonneuse fever (BF) caused by Rickettsia conorii . Methods : Sera from 500 Sicilian patients with confirmed BF were studied at the time of diagnosis and every week after treatment, and after recovery for the presence of various inflammatory mediators. Tumour necrosis factor α (TNFα), interleukin(IL)-6, IL-1α, IL-8, soluble TNF receptors (sTNF-R) and sIL-6R were assayed by commercially ELISA kits. C3, C4, factor B, C-reactive protein (CRP), fibrinogen, ceruloplasmin (Cp) and α 1 -antitrypsin (AAT) were assayed by a rate nephelometry. Results : Interferon gamma (I…

In vitro effects of aminobisphosphonates on Vgamma9Vdelta2 T cell activation and differentiation.

In vitro effects of aminobisphosphonates on Vgamma9Vdelta2 T cell activation and differentiation.

In this study we have evaluated the in vitro effects of four different aminobisphosphonates, alendronate, risedronate, neridronate and zoledronate, on Vγ9Vδ2 T cell activation and differentiation. All tested aminobisphosphonates induce an IL-2-dependent activation and expansion of Vγ9Vδ2 T lymphocytes in primary PBMC cultures of healthy donors. Most notably, they also determine a different distribution of Vγ9Vδ2 T cell subsets, with decrease of Tnaive and TCM cells and increase of TEM and TEMRA Vγ9Vδ2 cells, indicating that in vitro treatment with aminobisphosphonates induces Vγ9Vδ2 T lymphocytes to differentiate towards an effector/cytotoxic phenotype. Accordingly, Vγ9Vδ2 T lymphocytes cu…

Reciprocal stimulation of gammadelta T cells and dendritic cells during the anti-mycobacterial immune response.

Gammadelta T cells and dendritic cells (DC) are two distinct cell types of innate immunity that participate in early phases of immune response against Mycobacterium tuberculosis infection. Here we show that a close functional relationship exists between these cell populations. Using an in vitro coculture system, Vgamma1 T cells from Tcrb(-/- )mice were found to be activated by DC infected in vitro with BCG, as indicated by the elevated CD69 expression, IFN-gamma secretion and cytotoxic activity. This activation process was due to a non-cognate mechanism since it required neither cell to cell contact nor interaction between the TCR and a specific antigen, but was mediated by DC-derived IL-12…

Association between the HLA-DR alleles and longevity: a study in Sardinian population

Human longevity may be correlated with optimal functioning of the immune system, suggesting that genetic determinants of longevity also resides in those polymorphisms for the immune system genes that regulate immune responses as histocompatibility (HLA) antigens. However, conflicting results have been obtained. Some well planned and designed association studies performed in Caucasians suggest that longevity is associated with positive selection of alleles (i.e. HLA-DR11) or haplotypes (i.e. HLA-B8,DR3) that confer resistance to infectious diseases, respectively, via peptide presentation or via antigen non-specific control of immune response. Association studies are subjected to a number of …

Effects of chemically modified tetracyclines (CMTs) in sensitive, multidrug resistant and apoptosis resistant leukaemia cell lines

Recently discovered chemically modified tetracyclines (CMTs) have shown in vitro and in vivo anti-proliferative and anti-tumour activities. Here, we evaluated in vitro the anti-proliferative and apoptotic activity of six different dedimethylamino chemically modified tetracyclines (CMT-1, CMT-3, CMT-5, CMT-6, CMT-7 and CMT-8) in sensitive and multidrug resistant myeloid leukaemia cells (HL60 and HL60R) in vitro. Three of these compounds (CMT-5, CMT-6, CMT-7) showed low cytotoxic activity both in sensitive and in resistant cells, CMT-3 was endowed with a high anti-proliferative activity only in sensitive cells and was moderately effective as apoptosis inducing agent, with an activity similar …

IL-15, as IFN-gamma, induces the killing of Leishmania infantum in PMA-activated macrophages increasing IL-12

Impact of Heavy Polypropylene Mesh and Composite Light Polypropylene and Polyglactin 910 on the Inflammatory Response

The aim of the study was to analyze the acute inflammatory response after implantation of a heavyweight mesh of polypropylene (PP) compared with a composite mesh of light PP and polyglactin 910 (PG) in patients undergoing inguinal hernioplasty. A total of 30 male patients with inguinal hernia were included in the study and divided into 2 groups (PP and PP-PG) according to the mesh used. Changes of leukocytes, cytokines, growth factors, and acute phase proteins were evaluated in the sera. Leukocytes and acute phase proteins were significantly increased postoperatively in both groups, and the values were slightly higher in the PP group. Cytokine levels were significantly increased postoperat…

Tension-free hernia repair is associated with an increase in inflammatory response markers against the mesh.

Abstract Background: The purpose of this study was to evaluate the involvement of inflammatory mediators in patients undergoing Lichtenstein tension-free hernioplasty (LH) using polypropylene prosthetic materials or conventional Bassini hernia repair (BH). Methods: Thirty patients male with unilateral inguinal hernia without complications or recurrence were included in this study. Randomly, patients underwent LH or BH. Peripheral venous bloods samples were collected 24 hours prior to surgery and then 6, 24, 48 and 168 hours postoperatively. Results: We present evidences that LH patients showed a higher increased serum level of fibrinogen, C-reactive protein, alpha-1-antitrypsin, and interle…

Sex hormones modulate inflammatory mediators produced by macrophages.

Cytokines and growth factors in wound drainage fluid from patients undergoing incisional hernia repair.

Knowing the dynamics of growth factor and cytokine secretion within the site of a surgical operation is important, as they play a crucial role in the pathophysiology of wound healing and are a target for modifying the repair response. The aim of this study was to evaluate the production of several cytokines and growth factors in the drainage wound fluid from patients undergoing incisional hernia repair: namely, interleukin (IL)-6, IL-10, IL-1alpha, IL-1 ra, interferon-gamma, vascular endothelial growth factors and basic fibroblast growth factor. Ten female patients with abdominal midline incisional hernia undergoing surgical repair were included in this study. In all cases, a closed-suction…

CD4+ CCR5+ and CD4+ CCR3+ lymphocyte subset and monocyte apoptosis in patients with acute visceral leishmaniasis

The potential involvement of apoptosis in the pathogenesis of visceral leishmaniasis (VL) was examined by studying spontaneous and Leishmania antigen (LAg)-induced apoptosis using cryopreserved peripheral blood mononuclear cells (PBMC) of Sicilian patients with VL. Results indicate that monocytes and T lymphocytes from acute VL patients show a significantly higher level of apoptosis compared with that observed in healed subjects. The percentage of apoptotic cells was higher in monocytes than in T lymphocytes. T cells involved in programmed cell death (PCD) were mainly of the CD4(+) phenotype. In particular, the T helper 1-type (Th1) subset, as evaluated by chemokine receptor-5 (CCR5) expres…

IL-15 in human visceral leishmaniasis caused byLeishmania infantum

SummaryInterleukin (IL)-15 is a recently discovered cytokine with the ability to stimulate the proliferation activity of Th1 and/or Th2 lymphocytes. Here, we investigated the involvement of IL-15 in the immune response to Leishmania infantum infection by studying patients with visceral leishmaniasis (VL). We found that IL-15 is produced by leishmanial antigen (LAg)-stimulated peripheral blood mononuclear cells (PBMC) from active VL patients at a significantly higher level than those produced by cells from healed VL subjects or healthy controls. A significant increase in IL-15 serum blood levels was also observed in acute VL patients compared with healed ones. Furthermore, recombinant IL-15 …

Modifications in the production of cytokines and growth factors in drainage fluids following mesh implantation after incisional hernia repair

Abstract Background The aim of this study was to evaluate changes in the production of some cytokines (interleukins [ILs]-6, -10, -1, and -1ra), vascular endothelial growth factor, and beta-fibroblast growth factor after polypropylene mesh implantation. Methods Twenty female patients were divided into 2 groups. In 1 group, hernia repair was performed with conventional sutures (CR), whereas in the other group polypropylene mesh (MR) was used. Growth factors and cytokines production was analyzed in wound drain fluids based on the amount produced during 24 hours. Results IL-1 increased substantially in MR patients on postoperative days 1 and 2. IL1-ra and IL-10 production was always significan…

Anti-inflammatory effects of chemically modified tetracyclines by the inhibition of nitric oxide and interleukin-12 synthesis in J774 cell line

We investigated the effects of chemically modified tetracyclines (CMTs) on the production of nitric oxide (NO) and on the synthesis of some cytokines: tumour necrosis factor alpha (TNF-alpha), interleukin(IL)-10 and IL-12 in lipopolysaccharide (LPS)-treated J774 cell line. Furthermore, we studied the ability of these drugs to modify the viability in LPS-stimulated J774 macrophages. CMTs decreased, in a dose-dependent manner, inducible NO synthase (iNOS) activity and, consequently, nitrite formation in J774 cultures. The CMT-induced decrease in NO production is due to the inhibition of enzyme activity rather than to a direct effect on enzyme expression. The absence of the inhibition in mRNA …

Differentiation of human Vgamma9 Vdelta 2 T cell subsets by antigen or homeostatic cytokines

Chemically modified tetracyclines induce cytotoxic effects against J774 tumour cell line by activating the apoptotic pathway

Here, we have studied the effects of chemically modified tetracyclines (CMTs) on apoptosis both at the level of the cytoplasmic proteolytic caspase cascade, and on Bcl-2 and c-myc mRNA expression in the J774 macrophage cell line. The results indicate that CMTs induce morphological changes consistent with apoptotic events, as clearly demonstrated both by the acridine orange and ethidium bromide staining, and by TUNEL and fragmentation ELISA assays. Furthermore, the analysis of the cell cycle by flow cytometry shows an evident apoptotic sub-G0G1 peak, without important modifications in the cell cycle distribution. CMTs induce programmed cell death (PCD) in a dose-dependent manner and CMT-8 is…

Differentiation of human CD8+ T cells in BCG vaccinated and tuberculous patients.

Differential requirements for antigen or homeostatic cytokines for proliferation and differentiation of human Vgamma9Vdelta2 naive, memory and effector T cell subsets.

We have compared four human subsets of Vgamma9Vdelta2 T cells, naive (T(naive), CD45RA(+)CD27(+)), central memory (T(CM), CD45RA(-)CD27(+)), effector memory (T(EM), CD45RA(-)CD27(-)) and terminally differentiated (T(EMRA), CD45RA(+)CD27(-)), for their capacity to proliferate and differentiate in response to antigen or homeostatic cytokines. Cytokine responsiveness and IL-15R expression were low in T(naive) cells and progressively increased from T(CM) to T(EM) and T(EMRA) cells. In contrast, the capacity to expand in response to antigen or cytokine stimulation showed a reciprocal pattern and was associated with resistance to cell death and Bcl-2 expression. Whereas antigen-stimulated cells a…

Production of VEGF and b-FGF in the drainage fluid from patients undergoing incisional hernia repair

Wound healing is a complex process involving interaction between different cell types, such as growth factors. Among these, vascular endothelial growth factors (VEGF) and basic fibroblast growth factors (b-FGF) are the most important. The aim of this study was to assess the production of VEGF and b-FGF in wound drainage fluid from patients undergoing incisional abdominal hernia repair. Ten female patients with abdominal midline incisional hernia undergoing surgical repair were included in this study. In all cases a closed suction drain was placed in the wound below the fascia and removed on postoperative day 4. Wound fluid was collected on the I, II, III and IV day and its amount at each ti…

Apoptosi dei subsets linfocitari CD4+/ CCR5+, CD4+/ CCR3+ e dei monociti in pazienti con leishmaniasi viscerale acuta

Interleukin-15, as Interferon-gamma, Induces the Killing of Leishmania infantum in Phorbol-Myristate-Acetate-Activated Macrophages Increasing Interleukin-12

The potential leishmanicidal activity of interleukin-15 (IL-15) was examined while priming with the cytokine phorbol-myristate-acetate (PMA)-activated macrophages and infecting them with Leishmania infantum parasites. The activation of macrophage cultures with IL-15 determined a significant anti-leishmanial activity, comparable with that induced by interferon-gamma (IFN-gamma). The killing of Leishmania in macrophages primed with IL-15, as well as with IFN-gamma, was followed by an increase in the IL-12 synthesis. The neutralization of IL-15 or IFN-gamma, by specific monoclonal antibodies (MoAb) caused a significant reduction in leishmanicidal activity. Furthermore, in PMA-activated macroph…

Differential requirements for antigen or homeostatic cytokines for proliferation and differentiation of human Vgamma9Vdelta2 naive, memory and effector T cell subsets.

We have compared four human subsets of Vgamma9Vdelta2 T cells, naive (T(naive), CD45RA(+)CD27(+)), central memory (T(CM), CD45RA(-)CD27(+)), effector memory (T(EM), CD45RA(-)CD27(-)) and terminally differentiated (T(EMRA), CD45RA(+)CD27(-)), for their capacity to proliferate and differentiate in response to antigen or homeostatic cytokines. Cytokine responsiveness and IL-15R expression were low in T(naive) cells and progressively increased from T(CM) to T(EM) and T(EMRA) cells. In contrast, the capacity to expand in response to antigen or cytokine stimulation showed a reciprocal pattern and was associated with resistance to cell death and Bcl-2 expression. Whereas antigen-stimulated cells a…

MODIFIFICATIONS IN THE PRODUCTION OF CYTOKINES AND GROWTH FACTORS IN THE DRAINAGE FLUIDS FOLLOWING MESH IMPLANTATION AFTER INCISIONAL HERNIA REPAIR

HUMAN MEMORY VGAMMA9 VDELTA2 T CELLS REQUIRE HOMEOSTATIC CYTOKINES FOR PROLIFERATION AND DIFFERENTIATION.

Anti-inflammatory effects of annexin-1: stimulation of IL-10 release and inhibition of nitric oxide synthesis.

Annexin-1 (ANX-1) is an anti-inflammatory protein induced by glucocorticoids. Like glucocorticoids, ANX-1 and derived peptides inhibit eicosanoid synthesis, block leukocyte migration and induce apoptosis of inflammatory cells. Cytokines may possess either pro-inflammatory, i.e. interleukin(IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-12 or anti-inflammatory properties, i.e. IL-4, IL-10. The experiments described in the present study have been performed to answer the question whether the anti-inflammatory action of ANX-1 may be mediated, at least in part, by the release of IL-10. In macrophage (J774) cell line cultures primed with lipolysaccharide (LPS), recombinant ANX-1 stimulated IL-1…

Production of cytokines at the operation site

BACKGROUND AND AIM: Cytokines are part of a family of molecules involved in the initiation, control and termination of the events that occurs in wound healing process. Aim of this study was to evaluate the production of some cytokines [interleukin (IL)-6, IL-10, IL-1alpha, IL-1ra, interferon (IFN)-gamma] in the drainage wound fluid from patients undergoing incisional hernia repair. METHODS: Ten female patients with abdominal midline incisional hernia undergoing to surgical repair were included in this study. In all cases a closed suction drain was placed in the wound below the fascia and it was removed on the 4th postoperative day. Wound fluid was collected on the 1st, 2nd, 3rd and 4th day …