IgE-mediated basophil tumour necrosis factor alpha induces matrix metalloproteinase-9 from monocytes.

BACKGROUND: IgE-mediated activation of mast cells has been reported to induce the release of tumour necrosis alpha (TNF-α), which may display autocrine effects on these cells by inducing the generation of the tissue remodelling protease matrix metalloproteinase-9 (MMP-9). While mast cells and basophils have been shown to express complementary and partially overlapping roles, it is not clear whether a similar IgE/TNF-α/MMP-9 axis exists in the human basophil. The purpose of this study was thus to investigate whether IgE-mediated activation of human basophils induces TNF-α and MMP-9 release. METHODS: Human peripheral blood mononuclear cells (PBMC), isolated basophils and monocytes were stimulated up to 21 h with anti-IgE. Mediator releases were assessed by ELISA, and surface expressions of mediators were detected by flow cytometry. Upregulation of cytokine production was detected by Western blot and polymerase chain reaction (PCR). RESULTS: IgE-mediated activation of basophils induced the synthesis and release of both TNF-α and MMP-9 from PBMC. In contrast, IgE-mediated activation of purified basophils induced the release and cellular expression of TNF-α but not MMP-9. Isolated monocytes did not release MMP-9 upon anti-IgE stimulation, but MMP-9 release was induced by stimulating monocytes with supernatants from activated basophils, and this release was inhibited by anti-TNF-α neutralizing antibodies. CONCLUSION: Our results strongly indicate that human basophils release TNF-α following IgE-dependent activation and that this cytokine subsequently stimulates MMP-9 release from monocytes. These findings support a direct involvement of basophils in inflammation as well as suggesting a role for the basophil in tissue remodelling.

Mechanisms of hypoxic signal transduction regulated by reactive nitrogen species.

Recent reports devoted to the field of oxygen sensing outline that signalling molecules such as nitric oxide/nitric oxide derived species as well as cytokines and other inflammatory mediators participate in hypoxic signal transduction. In the present review, we summarize the current knowledge about the role of nitric oxide and reactive nitrogen species (RNS) derived from it in hypoxic signal transduction and particularly in accumulation/de-accumulation of hypoxia inducible factor 1 alpha (HIF-1alpha) protein, which is critical not only for cellular adaptation to low oxygen availability but also for generation of inflammatory and innate immune responses. After brief description of nitric oxide and other RNS as multifunctional messengers we analyse and discuss the RNS-dependent accumulation of HIF-1alpha protein under normoxia followed by discussion of the mechanisms of nitric oxide (NO)-dependent enzyme-regulated degradation of HIF-1alpha protein under low oxygen availability.

Role of MAP kinase-dependent apoptotic pathway in innate immune responses and viral infection.

Mitogen-activated protein (MAP) kinase cascades are multifunctional signalling networks that influence cell growth, differentiation, apoptosis and cellular responses to stress. Apoptosis signal-regulating kinase 1 (ASK1) is a MAP kinase kinase kinase that triggers apoptogenic kinase cascade leading to the phosphorylation/activation of c-Jun N-terminal kinases (JNK) and p38-MAP kinase, which are responsible to induce apoptotic cell death. This pathway plays a pivotal role in the transduction of signals from different apoptotic stimuli. Recently, it has become evident that ASK1 and its downstream pathway are employed in the transduction of signals from Toll-like receptors (TLR) - multistep processes that interfere with different intracellular signalling pathways. TLR are the key proteins that allow mammals to detect pathogens and mediate innate immune responses. In addition, ASK1 and its downstream pathway play a target role in the regulation of apoptosis in some cases of viral infection - AIDS, influenza, hepatitis C and others. In the present review, we summarize current knowledge about the role of ASK1 and its downstream pathway in innate immune responses and viral infection.

[Aromatase: universal and complex enzymology].

Cytochrome P-450 aromatase (cytochrome P-450 XIXA1, EC 1.14.14.1) is a key enzyme of estrogen biosynthesis. This is the only enzyme that catalyzes the processes leading to aromatization of the first ring of the steroid nucleus, and, therefore, gives rise to estrogens - estrone, estradiol and estriol. Other estrogens - estriol, equiline and equilenine - are formed mainly by hydroxylation or dehydrogenation of estradiol, so aromatase can be considered the only enzyme that limits the formation of estrogen.

The effect of CoCl2 on xanthine oxidase, nitric oxide synthase, and protein kinase C activity as well as cytochrome P450 1A1, 1A2 and 1B1 quantities in rat liver.

Established that CoCl2 induced oxidative stress activates xanthine oxidase, inhibit nitric oxide synthase and cytochrome P450 in the rat liver in vivo. The concentration of S-nitrosothiols was respectively decreased and PKC was activated. The quantities of general cytochrome P450 as well as its 1A1, 1A2 and 1B1 isoforms were decreased.

Activities of apoptotic signal 1-regulating protein kinase and poly-(ADP-ribose) polymerase and internucleosomal DNA fragmentation in rat liver during oxidative stress induced by cobalt chloride.

We revealed activation of apoptotic signal 1-regulating protein kinase, inhibition of poly-(ADP-ribose) polymerase, and intensification of internucleosomal DNA fragmentation in rat liver during oxidative stress induced by cobalt chloride.

Genistein effect on xanthine oxidase activity.

Genistein was defined to be an allosteric xanthine oxidase inhibitor in the concentrations 0.1-4.0 microM and xanthine oxidase activator with superoxide scavenging activity in the concentrations 5.0 microM and higher. But the most effective allosteric binding with the highest affinity was observed in the genistein concentrations 0.1-1.0 microM. Intraperitoneum injections of genistein (500 micrograms/kg) during three days with the interval 24 hours decrease xanthine oxidase activity in the liver, lung and brain of the Vistar rats.

In vitro effects of corticosteroids, DDT, and 4, 9-dichlorodibenzodioxin on rat liver xanthine oxidase activity. Interactions between xanthine oxidase and cytochrome P450 in rat liver in vivo.

It was established that deoxycorticosterone, cortisol, dexamethasone, DDT, and 4,9-dichlorodibenzodioxin inhibit in vitro binding of xanthine to highly purified rat liver xanthine oxidase. They are suggested to be allosteric inhibitors. The corresponding inhibition and binding constants were estimated. Also established was that cortisol and DDT, in dose 20 mg per kg of weight, inhibit xanthine oxidase and increase microsomal cytochrome P450 level in rat liver. There is an inverse relationship between xanthine oxidase activity and cytochrome P450 level in rat liver.