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Secreted Cytokines (secreted + cytokine)
Selected AbstractsThe tale of transforming growth factor-beta (TGF,) signaling: A soigné enigmaIUBMB LIFE, Issue 10 2009Arindam Chaudhury Abstract Transforming growth factor-beta (TGF,) is a secreted cytokine, which intricately controls a plethora of physiological and pathological processes during development and carcinogenesis. TGF, exerts antiproliferative effects and functions as a tumor suppressor during early stages of tumorigenesis, whereas at later stages it functions as a tumor promoter aiding in metastatic progression through an autocrine TGF, loop. Intricate knowledge of TGF, signaling and its regulation are still evolving. In this review, we make an attempt to showcase the associated enigma of TGF, signaling in its dual functional role as tumor suppressor and metastatic promoter during early and late stages of carcinogenesis, respectively. © 2009 IUBMB IUBMB Life, 61(10): 929,939, 2009 [source] Long-term effects of idiotype vaccination on the specific T-cell response in peripheral blood and bone marrow of multiple myeloma patientsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2007Amir Osman Abdalla Abstract Objectives:, To elucidate long-term effects of idiotype (Id) vaccination on Id-specific T cells of multiple myeloma (MM) patients and compare Id-specific T-cell responses of peripheral blood with those of bone marrow (BM). Materials and methods:, Id-specific T-cell responses of peripheral blood mononuclear cells (PBMC) were compared with those of BM mononuclear cells (BMMC) in 10 MM patients vaccinated with the Id protein at a median time of 41 months since the last immunization. The PBMC responses at late follow-up were also compared with those during active immunization. The responses were assessed by a proliferation assay, enzyme-linked immunospot (ELISPOT) (,-interferon), cytometric bead array (CBA) for secreted cytokines and quantitative real-time polymerase chain reaction (QRT-PCR) for cytokine gene expression. Results:, At the late testing time, an Id-specific response was detected in PBMC of five patients (ELISPOT, CBA, QRT-PCR) and in BMMC of four patients (CBA, QRT-PCR). A response in both compartments was noted only in three patients. The cytokines gene profile was consistent with a predominance of Th2 cells [interleukin (IL)-4, IL-5, IL-10]. Comparison of the Id-specific responses of PBMC during active immunization with those at the late follow-up showed that the frequency and magnitude of the responses had decreased significantly by time (proliferation/ELISPOT) (P < 0.02) and shifted at the gene level from a Th1 to a Th2 profile (P < 0.05). Conclusion:, Id-specific T cells may decline overtime and shift toward a Th2 response and may be found at a similar frequency of patients in blood and BM. [source] Mechanisms of immune suppression by interleukin-10 and transforming growth factor-,: the role of T regulatory cellsIMMUNOLOGY, Issue 4 2006Alison Taylor Summary Specific immune suppression and induction of tolerance are essential processes in the regulation and circumvention of immune defence. The balance between allergen-specific type 1 regulatory (Tr1) cells and T helper (Th) 2 cells appears to be decisive in the development of allergy. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals. In contrast, there is a high frequency of allergen-specific interleukin-4 (IL-4)-secreting T cells in allergic individuals. Allergen-specific immunotherapy can induce specific Tr1 cells that abolish allergen-induced proliferation of Th1 and Th2 cells, as well as their cytokine production. Tr1 cells utilize multiple suppressor mechanisms, such as IL-10 and transforming growth factor-, (TGF-,) as secreted cytokines and various surface molecules, such as cytotoxic T-lymphocyte antigen 4 and programmed death-1. IL-10 only inhibits T cells stimulated by low numbers of triggered T-cell receptors, which depend on CD28 costimulation. IL-10 inhibits CD28 tyrosine phosphorylation, preventing the binding of phosphatidylinositol 3-kinase p85 and consequently inhibiting the CD28 signalling pathway. In addition, IL-10 and TGF-, secreted by Tr1 cells skew the antibody production from immunoglobulin E (IgE) towards the non-inflammatory isotypes IgG4 and IgA, respectively. Induction of antigen-specific Tr1 cells can thus re-direct an inappropriate immune response against allergens or auto-antigens using a broad range of suppressor mechanisms. [source] Roles of bone morphogenetic protein signaling and its antagonism in holoprosencephaly,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2010John Klingensmith Abstract Holoprosencephaly (HPE) is the most common malformation of the forebrain, resulting from a failure to completely septate the left and right hemispheres at the rostral end of the neural tube. Because of the tissue interactions that drive head development, these forebrain defects are typically accompanied by midline deficiencies of craniofacial structures. Early events in setting up tissue precursors of the head, as well as later interactions between these tissues, are critical for normal head formation. Defects in either process can result in HPE. Signaling by bone morphogenetic proteins (BMPs), a family of secreted cytokines, generally plays negative roles in early stages of head formation, and thus must be attenuated in multiple contexts to ensure proper forebrain and craniofacial development. Chordin and Noggin are endogenous, extracellular antagonists of BMP signaling that promote the normal organization of the forebrain and face. Mouse mutants with reduced levels of both factors display mutant phenotypes remarkably analogous to the range of malformations seen in human HPE sequence. Chordin and Noggin function in part by antagonizing the inhibitory effects of BMP signaling on the Sonic hedgehog and Nodal pathways, genetic lesions in each being associated with human HPE. Study of Chordin;Noggin mutant mice is helping us to understand the molecular, cellular, and genetic pathogenesis of HPE and associated malformations. © 2010 Wiley-Liss, Inc. [source] ORIGINAL ARTICLE: Characterization of Cytokine Production by Human Term Placenta Macrophages In VitroAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2008Oleg Pavlov Problem, Macrophages are apparently the only immune cells within placenta villi, yet functions of these cells remain obscure. It has been postulated that placental macrophages accomplish regulatory roles at the fetal,maternal interface by means of wide variety of secreted cytokines. We attempt to analyze the patterns of cytokine production in an isolated population of placental macrophages. Method of study, Macrophages were obtained from term placentas in the absence of spontaneous labor. The basal and lipopolysaccharide (LPS)-stimulated levels of intracellular cytokines were detected by flow cytometry. The basal cytokine secretion was determined by BDÔCytometry Bead Array (BD Biosciences, San Diego, CA, USA). Results, Intracellular IL-1,, IL-1,, IL-6, and TNF, were detected in 31, 27, 4, and 3% CD68+ cells, respectively. Stimulation with LPS increased the proportions of cytokine-producing CD68+ cells to 48, 50, 28, and 49%, respectively. Under basal conditions, levels of released TNF, and IL-6, respectively, were 20- and 25-fold higher when compared with IL-1, while IL-10 was secreted in small but detectable amounts. When a secretory activity was estimated for cytokine-producing cells, the secretion rate for TNF, and IL-6 overwhelmingly surpassed that for IL-1, (TNF,:IL-6:IL-1, ratio was 192:145:1). Conclusion, These results suggest functional heterogeneity of the placental macrophage population and contribute to the elucidation of regulatory roles of these cells in gestation. [source] Regulation of global gene expression in the bone marrow microenvironment by androgen: Androgen ablation increases insulin-like growth factor binding protein-5 expressionTHE PROSTATE, Issue 15 2007Chang Xu Abstract BACKGROUND Prostate cancer frequently metastasizes to bone. Androgen suppression treatment is initially highly effective, but eventually results in resistant cancer cells. This study evaluates the effects of androgen suppression on the bone and bone marrow (BM). In particular we questioned whether the androgen therapy could adversely facilitate prostate cancer progression through an increase growth factor secretion by the bone microenvironment. METHODS Global gene expression is analyzed on mPEDB DNA microarrays. Insulin-like growth factor binding protein-5 (IGFBP5) is detected by immunohistochemistry in mouse tissues and its regulation measured by qPCR and Western blotting in human BM stromal cells. Effects of extracellular matrix-associated IGFBP5 on human prostate epithelial cells are tested in an MTS cell-growth assay. RESULTS Castration increases expression of 159 genes (including 4 secreted cytokines) and suppresses expression of 84 genes. IGFBP5 is most consistently increased and the increase in expression is reversed by testosterone administration. IGFBP5 protein is detected in vivo in osteoblasts, BM stromal cells, and endothelial cells. Primary human stromal cell cultures secrete IGFBP5. In vitro, treatment of immortalized human marrow stromal cells with charcoal-stripped serum increases IGFBP5 mRNA expression, which is reversed by androgen supplementation. IGFBP5 is incorporated into the extracellular matrix. Further, IGFBP5 immobilized on extracellular matrices of stromal cells enhances the growth of immortalized prostate epithelial cells. CONCLUSIONS Androgen suppressive therapy increases IGFBP5 in the BM microenvironment and thereby may facilitate the progression of prostate cancer. Prostate 67: 1621,1629, 2007. © 2007 Wiley-Liss, Inc. [source] Chemokine receptors in cancer metastasis and cancer cell-derived chemokines in host immune responseCANCER SCIENCE, Issue 11 2007Keiichi Koizumi The chemotactic cytokines called chemokines are a superfamily of small secreted cytokines that were initially characterized through their ability to prompt the migration of leukocytes. Attention has been focused on the chemokine receptors expressed on cancer cells because cancer cell migration and metastasis show similarities to leukocyte trafficking. CXC chemokine receptor 4 (CXCR4) was first investigated as a chemokine receptor that is associated with lung metastasis of breast cancers. Recently, CXCR4 was reported to be a key molecule in the formation of peritoneal carcinomatosis in gastric cancer. In the present review, we highlight current knowledge about the role of CXCR4 in cancer metastases. In contrast to chemokine receptors expressed on cancer cells, little is known about the roles of cancer cell-derived chemokines. Cancer tissue consists of both cancer cells and various stromal cells, and leukocytes that infiltrate into cancer are of particular importance in cancer progression. Although colorectal cancer invasion is regulated by the chemokine CCL9-induced infiltration of immature myeloid cells into cancer, high-level expression of cancer cell-derived chemokine CXCL16 increases infiltrating CD8+ and CD4+ T cells into cancer tissues, and correlates with a good prognosis. We discuss the conflicting biological effects of cancer cell-derived chemokines on cancer progression, using CCL9 and CXCL16 as examples. (Cancer Sci 2007; 98: 1652,1658) [source] | |||||||||||||