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Strong Inhibitory Effects (strong + inhibitory_effects)
Selected AbstractsEffects of possible endocrine disruptors on MyD88-independent TLR4 signalingFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2008Takahiro Ohnishi Abstract Endocrine disrupting chemicals (EDCs) may potentially worsen infectious diseases because EDCs disturb human immune function by interfering with endocrine balance. To evaluate the influence of EDCs on the innate immune function of macrophages, we investigated the effects of 37 possible EDCs on lipopolysaccharide-induced activation of the IFN-, promoter. Alachlor, atrazine, benomyl, bisphenol A, carbaryl, diethyl phthalate, dipropyl phthalate, kelthane, kepone, malathion, methoxychlor, octachlorostyrene, pentachlorophenol, nonyl phenol, p -octylphenol, simazine and ziram all inhibited the activation. Kepone and ziram showed strong inhibitory effects. Aldicarb, amitrole, benzophenone, butyl benzyl phthalate, 2,4-dichlorophenoxy acetic acid, dibutyl phthalate, 2,4-dichlorophenol, dicyclohexyl phthalate, diethylhexyl adipate, diethylhexyl phthalate, dihexyl phthalate, di- n -pentyl phthalate, methomyl, metribuzin, nitrofen, 4-nitrotoluene, permethrin, trifluralin, 2,4,5-trichlorophenoxyacetic acid and vinclozolin had no significant effects at 100 ,M. These results indicate that some agrochemicals and resin-related chemicals may potentially inhibit macrophage function, which suggests that endocrine disruptors may influence the development of infectious diseases. [source] Retinoic acid induces expression of the interleukin-1, gene in cultured normal human mammary epithelial cells and in human breast carcinoma linesJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2002Limin Liu Retinoic acid (RA) and its derivatives inhibit the proliferation of normal human mammary epithelial cells (HMEC) and some breast carcinoma lines by mechanisms which are not fully understood. To identify genes that mediate RA-induced cell growth arrest, an HMEC cDNA library was synthesized and subtractive screening was performed. We identified the interleukin-1, (IL-1,) gene as an RA induced gene in HMEC. Northern blot analyses showed that the IL-1, gene was up-regulated as early as 2 h after RA treatment. Results from the treatment of HMEC with cycloheximide and actinomycin D indicated that the regulation of the IL-1, gene by RA occurred at the transcriptional level and that the IL-1, gene is a direct, downstream target gene of RA. To evaluate the effects of IL-1, on cell proliferation, the proliferation of HMEC was measured in the presence of RA or IL-1,, or both. Either RA or IL-1, could significantly inhibit the proliferation of HMEC. However, the addition of soluble IL-1 receptor antagonist (sIL-1ra) to the cell culture medium did not block RA-induced HMEC growth inhibition, whereas sIL-1ra did block the growth inhibition of HMEC by IL-1,. IL-1, expression was not observed in the three carcinoma cell lines, MCF-7, MDA-MB-231, and MDA-MB-468, as compared to the HMEC. Growth curves of the breast carcinoma cell lines showed strong inhibitory effects of RA and IL-1, on the growth of the estrogen receptor (ER) positive MCF-7 cell line, but only a small effect on the ER negative MDA-MB-231 cells. The expression of the IL-1, gene was also transcriptionally activated by RA in normal epithelial cells of prostate and oral cavity. Our results suggest that: (a) the IL-1, gene is a primary target of RA receptors in HMEC; (b) the enhanced expression of the IL-1, gene does not mediate the RA-induced growth arrest of HMEC; and (c) the expression of the IL-1, gene is low or absent in all three human breast carcinoma cell lines examined, but the defect in the IL-1, signaling pathway may be different in ER positive versus ER negative carcinoma cells. © 2002 Wiley-Liss, Inc. [source] Bis-(3-hydroxyphenyl) diselenide inhibits LPS-stimulated iNOS and COX-2 expression in RAW 264.7 macrophage cells through the NF- kB inactivationJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2009Kyung-Min Shin Abstract Objectives Previously, we reported that diaryl diselenide compounds have strong inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophages. In this study, we investigated the molecular mechanisms underlying NO suppression and prostaglandin E2 (PGE2) production by diaryl diselenide compounds, bis-(2-hydroxyphenyl) diselenide (DSE-A), bis-(3-hydroxyphenyl) diselenide (DSE-B), bis-(4-hydroxyphenyl) diselenide (DSE-C), dipyridyl diselenide (DSE-D) and diphenyl diselenide (DSE-E). Methods The effect of these compounds on NO suppression and PGE2 production was investigated in RAW 264.7 macrophages. Key findings Our data indicate that of the above, DSE-B most potently inhibits NO and PGE2 production, and that it also significantly reduces the releases of tumour necrosis factor (TNF)-,, interleukin(IL)-1, and IL-6. Consistent with these observations, DSE-B also reduced the protein levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), and the mRNA levels of iNOS, COX-2, TNF-,, IL-1, and IL-6. Furthermore, DSE-B inhibited LPS-induced nuclear factor-,B (NF-,B) activation, which was associated with the prevention of the inhibitor ,B-, (I,B-,) degradation and a subsequent reduction in nuclear p65 protein levels. Conclusions Taken together, our data suggest that the anti-inflammatory properties of DSE-B are due to reduction in the expression of iNOS, COX-2, TNF-,, IL-1, and IL-6 through the down-regulation of NF-,B binding activity. [source] Spasmolytic and antidiarrhoeal properties of the Yucatec Mayan medicinal plant Casimiroa tetrameriaJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2005Michael Heinrich The Maya of the Yucatán peninsula commonly use the leaves of Casimiroa tetrameria for treating gastrointestinal disorders, notably diarrhoea and dysentery, as well as gastrointestinal cramps. The phytochemical investigation resulted in the isolation of 13 compounds: eight polymethoxylated flavonoids (two as minor components with a main constituent), four flavonoid glycosides and one furanocoumarin. In this study we used two well-established models in order to assess the gastrointestinal effects of C. tetrameria extracts and isolated compounds: the USSING-chamber, a pharmacological model for diarrhoea, and the isolated guinea pig ileum, a model for modulatory effects on ileum contraction. Extracts and the class of polymethoxylated flavonoids showed strong inhibitory effects in both models, which provides ex-vivo evidence for the use of this botanical drug in the treatment of several gastrointestinal problems, most notably diarrhoea. The crude extract, polymethoxylated flavonoid-rich fractions and the polymethoxylated flavonoids tested showed prominent antisecretory activity. Polymethoxylated flavonoid-rich fractions also inhibited the histamine-induced contractions in the guinea pig model. The effects are not due to a single compound, but to a large number of structurally related compounds that all contribute to the effect. [source] An approach to characterizing single-subunit mutations in multimeric prepores and pores of anthrax protective antigenPROTEIN SCIENCE, Issue 2 2009Blythe E. Janowiak Abstract Heptameric pores formed by the protective antigen (PA) moiety of anthrax toxin translocate the intracellular effector moieties of the toxin across the endosomal membrane to the cytosol of mammalian cells. We devised a protocol to characterize the effects of individual mutations in a single subunit of heptameric PA prepores (pore precursors) or pores. We prepared monomeric PA containing a test mutation plus an innocuous Cys-replacement mutation at a second residue (Lys563, located on the external surface of the prepore). The introduced Cys was biotinylated, and the protein was allowed to cooligomerize with a 20-fold excess of wild-type PA. Finally, biotinylated prepores were freed from wild-type prepores by avidin affinity chromatography. For the proof of principle, we examined single-subunit mutations of Asp425 and Phe427, two residues where Ala replacements have been shown to cause strong inhibitory effects. The single-subunit D425A mutation inhibited pore formation by >104 and abrogated activity of PA almost completely in our standard cytotoxicity assay. The single-subunit F427A mutation caused ,100-fold inhibition in the cytotoxicity assay, and this effect was shown to result from a combination of strong inhibition of translocation and smaller effects on pore formation and ligand affinity. Our results show definitively that replacing a single residue in one subunit of the heptameric PA prepore can inhibit the transport activity of the oligomer almost completely,and by different mechanisms, depending on the specific residue mutated. [source] Acylated Flavonol Bisdesmosides, Sinocrassosides A3,A7 and B3, with Aminopeptidase N Inhibitory Activity from Sinocrassula indica,CHEMISTRY & BIODIVERSITY, Issue 3 2009Toshio Morikawa Abstract Six new acylated flavonol bisdesmosides, sinocrassosides A3, A4, A5, A6, A7, and B3 (1,6, resp.), were isolated from the MeOH extract of the whole plant of Sinocrassula indica. The structures of 1,6 were elucidated on the basis of chemical and physicochemical evidence. Among them, 2 and 6 which have an acyl group in the 3,,,-position were found to show strong inhibitory effects on aminopeptidase N activity, which were stronger than that of curcumin. [source] | |||||||||||||