Interaction between cytokines and 8-mercaptoguanosine in humoral immunity: synergy with interferon

In previous studies it has been demonstrated that a T cell-like differentiation signal is transmitted by C8-substituted guanine ribonucleosides such as 8-mercaptoguanosine (8MGuo) to antigen-stimulated B cells. A large subset of potentially reactive B cells remains unresponsive to antigen even in the presence of signals provided by these nucleosides except when this signal is preceded by a soluble activity present in mixed lymphocyte culture supernatants. Studies with purified preparations of interleukin (IL)-1, IL-2, IL-3, granulocyte-macrophage colony stimulating factor, B cell stimulatory factor 1 (IL-4), and B cell growth factor II (IL-5) indicated that none of these activities is capable of synergizing with 8MGuo to augment B cell responsiveness to antigen. Therefore, supernatants from a number of cloned cell lines were examined for activity that could synergize with 8MGuo, in order to determine the cellular source of this activity. Soluble products secreted by cloned 24/G1 T cells act synergistically with 8MGuo to evoke enhanced antibody responses to specific antigen in populations of purified B cells. Because concanavalin (Con) A-activated 24/G1 cells produce large quantities of interferon-gamma (IFN-gamma), the possibility that interferons might mediate synergy with 8MGuo was investigated. Purified murine IFN-gamma is unable to interact synergistically with 8MGuo; moreover, treatment of active 24/G1 supernatants with monoclonal anti-IFN-gamma antibodies or at pH 2 fails to abrogate their ability to synergize. In contrast to IFN-gamma, when B cells were supplemented with either IFN-alpha or IFN-beta, antigen-dependent synergy with 8MGuo was observed. However, abrogation of IFN-alpha and IFN-beta activity with specific antibodies fails to interfere with synergy between 8MGuo and mixed lymphocyte culture or Con A supernatants. Therefore, it appears that although IFN-alpha and IFN-beta are not responsible for the synergizing activity present in activated T cell supernatants, they nonetheless represent a previously unrecognized source of synergizing activity.     

C-type lectin receptors and cytokines in fungal immunity

Fungi are the cause of opportunistic infections, predominantly in immunocompromised individuals although, primary fungal infections can occur in apparently healthy individuals. Successful host defence requires an effective innate and adaptive immune response. Central to host immune responses are the induction of cytokines; the signals which help to activate the innate immune system and which play a central role in directing the development of pathogen-specific immunity. C-type lectins play a central role in the recognition and shaping of immune responses to fungal pathogens, in part, through the induction and modulation of cytokine responses. Understanding which cytokines induce protective responses to these pathogens and how C-type lectins and other receptors direct cytokine production may allow development of novel antifungal therapies. Here we review the C-type lectins, their influence on cytokine production and subsequent immune responses in antifungal immunity.     

Proinflammatory cytokines in antilipopolysaccharide immunity against Klebsiella infections

This study was undertaken in order to determine whether proinflammatory cytokines are involved in a previously described protection against Klebsiella infection mediated by antilipopolysaccharide antibodies. BALB/c mice were infected intraperitoneally with a lethal challenge of Klebsiella pneumoniae Caroli. One group of mice was protected with monoclonal antibodies against lipopolysaccharide prior to infection and the second was not. We determined the number of colony-forming units at different time points in the blood of infected animals and paralleled them with plasma levels of five proinflammatory cytokines measured by enzyme immunoassays. Our results show that the two groups of animals tested expressed different plasma concentrations for all cytokines. The greatest difference was detected 24 hours after infection, with a higher production in the unprotected group. We concluded that a reduced cytokine production is partially responsible for the survival of protected animals.     

Interrelationship between cyclic AMP level and chondrogenesis in vitro

A consistent chondrogenesis takes place in micro-mass cultures of stage 23-24 chicken limb bud mesenchymal cells. In these cultures a short, marked elevation of cAMP level was detected at the time of the onset of cartilage phenotype expression. On the other hand, exogeneous glycosaminoglycans which inhibited chondrogenesis caused a reduction in the cAMP level of the cells. These correlations between cAMP level and phenotypic characteristics suggest that, among other things required in chondrogenesis, cAMP level may be a prominent factor.     

WntD and Diedel: Two immunomodulatory cytokines in Drosophila immunity

Remarkable progress has been made on the understanding of the basic mechanisms of innate immunity in flies, from sensing infection to production of effector molecules. However, how the immune response is orchestrated at the level of the organism remains poorly understood. While cytokines activating immune responses, such as Spaetzle or Unpaired-3, have been identified and characterized in Drosophila, much less is known regarding immunosuppressor cytokines. In a recent publication, we reported the identification of a novel cytokine, Diedel, which acts as systemic negative regulator of the IMD pathway. Here, we discuss the similarities between Diedel and WntD, another immunomodulatory cytokine and present evidence that the 2 molecules act independently from one another.     

Signaling of interleukin-17 family cytokines in immunity and inflammation

IL-17 cytokine family, though still young since discovery, has recently emerged as critical players in immunity and inflammatory diseases. The prototype cytokine, IL-17A, plays essential roles in promoting inflammation and host defense. IL-17RA, a member of the IL-17 receptor family, forms a complex with another member, IL-17RC, to mediate effective signaling for IL-17A as well as IL-17F, which is most similar to IL-17A, via Act1 and TRAF6 factors. On the other hand, IL-17RA appears to interact with IL-17RB to regulate signaling by another cytokine IL-25. IL-25, the most distant from IL-17A in the IL-17 family, is involved in allergic disease and defense against helminthic parasites. In this review, we discuss recent advancements on signaling mechanisms and biological functions of IL-17A, IL-17F and IL-25, which will shed light on the remaining IL-17 family cytokines and help understand and treat inflammatory diseases.     

Interrelationship between lactate and cardiac fatty acid metabolism

This overview is presented, in the main, to summarize the following aspects of lactate and cardiac fatty acid metabolism: 1. The utilization of exogenous carbohydrates and fatty acids by the heart. 2. The competition between lactate and fatty acids in cardiac energy metabolism. 3. The effect of lactate on endogenous triacylglycerol homeostasis. 4. Lactate-induced impairment of functional recovery of the post-ischemic heart. 5. The effect of lactate on lipid metabolism in the ischemic and post-ischemic heart. 6. The consequences of hyperlactaemia for cardiac imaging.     

Interrelationship between the Bcg and Tbc-1 genes

The relationship of the mouse Bcg and Tbc-1 genes was studied. It was shown that the F1 hybrids between highly susceptible to tuberculosis mice I/St (Tbc-1s) and the Bcgs-carrying strains were highly resistant to M. tuberculosis H37Rv infection. These results point to complementation of Bcgs and Tbc-1s genes. Analysis of survival time of the [(AKR x B10-fzy)F1 x B10-Fzy]BC1 offspring showed that the mouse chromosome 1 does not regulate resistance to H37Rv infection. No linkage of the Tbc-1s gene with chromosome 1 was revealed when using fzy gene as a marker of the chromosome 1.     

Interrelationship between nuclear histone binding and cell proliferation

1. Binding of non-enzymatically [methyl-14C]-labeled histone H3 to nuclei isolated from young and old rat livers, regenerating rat liver, and tumor cells has been investigated. 2. Scatchard plot analysis indicated that various cell types had different binding capacity and different dissociation constant (Kd). 3. Nuclei isolated from younger rats had fewer binding sites and lower Kd (or higher Ka) values for [methyl-14C]H3 than those from older rats. 4. Fewer binding sites and lower Kd values were also observed with nuclei isolated from the maximally regenerating liver (24 hr after partial hepatectomy) and the fast-growing ascites tumor and Novikoff hepatomas. 5. These results strongly suggest that the number of binding sites and affinity of histone H3 for nuclei appears to be correlated with the degree of cell proliferation. 6. Fractionation of the [methyl-14C]H3 bound nuclei into nuclear membrane and nucleoplasm demonstrates that approx. 94% of radioactivity is associated with the former in which less than 6% of DNA is found, whereas 94% of total DNA is found in nucleoplasm. 7. This suggests that the binding of [methyl-14C]H3 to nuclei is independent of DNA present in each fraction.     

Interrelationship between nitric oxide and prostaglandins in bovine granulosa cells

It is well recognized that prostaglandins of the E (PGE) and F (PGF) series play an important role in ovarian physiology; in addition, nitric oxide (NO) has been recently demonstrated to be an important mediator of granulosa cell function. There is now evidence for a biologic relationship between PGs and the NO biosynthetic pathway. The aim of this study was to investigate the relationship between NO and PGE2 and PGF2alpha in bovine granulosa cells. Granulosa cells collected from small (<5mm) and large (>8mm) follicles were treated with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) or with indomethacin, an inhibitor of PGs synthesis, and PGE2 and PGF2alpha were quantified; in addition, the effects of PGE2 PGF2alpha and indomethacin on steroidogenesis and NO production were determined. The highest concentration of SNAP inhibited (P < 0.001) PGE2 production in cells from both kinds of follicles, while the lowest dose was effective only in cells from small follicles. The highest concentration of SNAP inhibited and stimulated (P < 0.001) PGF2alpha production in cells from small and large follicles, respectively. Progesterone (P4) production was stimulated by PGE2 and inhibited by PGF2alpha (P < 0.001) in cells from both types of follicles. Estradiol 17beta (E2) secretion was inhibited in cells from small and stimulated in those from large follicles by PGE2 (P < 0.05), while PGF2alpha was stimulatory in cells from both kinds of follicles (P < 0.001). P4 production by cells from small follicles was inhibited and stimulated by those from large follicles by indomethacin (P < 0.001), which also increased E2 output in cells from small follicles (P < 0.001). NO production was inhibited by both PGE2 and PGF2alpha except at the lowest concentration, which was stimulatory (P < 0.001). Indomethacin stimulated (P < 0.001) NO production. Taken together, the present data suggest a cross-talk between NO and PGs biosynthetic pathways, which needs to be further clarified.