Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The functional properties of infiltrating macrophages (Mphi) must be tightly regulated to facilitate appropriate responses to complex conditions in an inflammatory focus. This study was designed to ascertain whether uncommitted Mphi that have been exposed to combinations of cytokines with opposing functions develop properties dictated by one cytokine or by cytokine mixtures. Uncommitted rat bone marrow-derived Mphi (BMDMs) were incubated with IFN-gamma, TNF-alpha, TGF-beta, IL-4, IL-6, and IL-10 alone or sequentially in combinations. After 48 h, function was assessed by nitric oxide (NO) generation, uptake of apoptotic neutrophils, and beta-glucuronidase expression. IFN-gamma followed 4 h later by TNF-induced NO generation. The pretreatment of BMDMs before IFN-gamma priming with TNF, TGF-beta, and IL-4 suppressed NO generation by 87%, 92%, and 85%, respectively; IL-10 had no effect. The same cytokines administered at 4 h after IFN priming had no effect on NO generation. The uptake of apoptotic polymorphonuclear leukocytes was augmented by TNF (40% vs 29% controls; p < 0.05) and decreased by IFN-gamma, IL-10, and IL-4. The TNF response was unaffected by subsequent treatment with IFN-gamma, IL-4, or IL-10. Similarly, the decreased polymorphonuclear leukocyte uptake induced by IFN-gamma, IL-4, or IL-10 was unaffected by the subsequent addition of TNF. Beta-glucuronidase expression was increased by TGF-beta and decreased by IFN-gamma. These responses were not modified by cytokines with the opposing function. Thus, the functional response of BMDMs to complex mixtures of cytokines was determined by the first cytokine to which they were exposed. Once activated, BMDMs become unresponsive to alternative activating signals, a finding which has obvious implications for Mphi function in vivo.
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PMID:Initial cytokine exposure determines function of macrophages and renders them unresponsive to other cytokines. 971 70

Previous studies on a murine model have demonstrated that the administration of Lactobacillus helveticus and Lactobacillus casei inhibits the development of fibrosarcoma and colon carcinoma, respectively. The aim of this work was to study the beneficial effects of the consumption of milk fermented by L. helveticus on a murine model for mammary carcinoma. Female BALB/c mice were challenged by a single subcutaneous injection of tumoral cells (American Type Culture Collection 4T1) in the left mammary gland. Prior to tumour injection, mice were fed for two, five or seven consecutive days with fermented milk. The following factors were monitored for 2 months: rate of tumour development, histological studies, apoptosis, phagocytic index, peritoneal macrophages, determination of beta-glucuronidase enzyme in peritoneal macrophages, determination of gamma-interferon (INFgamma) and tumour necrosis factor-alpha (TNF-alpha) in blood serum, determination of CD4+, CD8+, interleukin-6 (IL-6), IL-10, TNF-alpha and INFgamma by immunoperoxidase, and measurement of beta-glucuronidase activity in intestinal fluid. The administration of L. helveticus delayed the development of the tumour in all cases, a 2- or 7-day feeding period being most effective. This work demonstrates that milk fermented with L. helveticus decreases the growth rate of mammary tumours. The effect was mediated by increased apoptosis and decreased production of pro-inflammatory cytokines, in particular IL-6, implicated in oestrogen synthesis.
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PMID:Effect of milk fermented with a Lactobacillus helveticus R389(+) proteolytic strain on the immune system and on the growth of 4T1 breast cancer cells in mice. 1683 Dec 11