[The role of glucocorticoid hormones in interleukin-1 signal transduction via the sphingomyelin pathway]. / Rol' gliukokortikoidnykh gormonov v transduktsii signala interleikina-1 po sfingomielinovomu puti.

Interleukin-1 and glucocorticoid hormones are the key transmitters of interaction between the neuroendocrine and immune systems. To study the molecular mechanisms of immunomodulatory effects of Interleukin-1 and glucocorticoid hormones, a search for changes in activity of neutral sphingomyelinase: the main marker of initiation of Interleukin-1beta signal transduction via the sphingomyelin pathway in target cells, was accomplished. The Interleukin-1beta was found to activate neutral sphingomyelinase both in P2 fraction of murine brain cortex and membranes of immune-competent cells. Experimental modifications of endogenous glucocorticoid level in the mouse blood were for the first time shown to induce changes in neutral sphingomyelinase activity in membranes of the cells of the immune and nervous systems. It appears that the sphingomyelinase pathway of Interleukin-1beta signaling might be a possible target for glucocorticoid hormones' immune-modulating effects.

[Glucocorticoid hormones in immunomodulating effect of defensins]. / Gliukokortikoidnye gormony v realizatsii immunomoduliruiushchego deistviia defensinov.

Defensins are a family of antimicrobial cationic peptides localized mainly in neutrophile granulocytes. The defensins are known to display corticostatic activity by means of suppression of stress- and ACTH-induced rise in corticosterone level in the blood. The present study examines influence of defensin fractions with different corticostatic activity on suppressor functions of T-lymphocytes. It was shown that corticostatic effects of defensins are revealed under an increased level of glucocorticoids in the blood after hydrocortisone application. Defensins were found to limit the inhibitory action of glucocorticoids on the suppressor functions of T-lymphocytes. After adrenalectomy this phenomenon was not observed.

[The role of neutral sphingomyelinase in the interleukin-1beta signal transduction in cells of the mouse cerebral cortex]. / Rol' neitral'noi sfingomielazy v transduktsii signala interleikina-1beta v kletkakh kory golovnogo mozga myshei.

Involvement of the sphingomyelin cascade in Interleukin 1 beta (IL-1) signal transduction pathway in membrane fraction P2 of the murine brain cortex, was found. A key role of the membrane enzyme neutral sphingomyelinase (nSMase) in triggering the sphingomyelin pathway for IL-1 beta, was confirmed. The IL-1 beta was shown to activate in a dose-dependent manner nSMase in the P2 fraction of the brain cortex. Employment of both brain cortex membranes from the mice deficient in the type I IL-1 receptor and of IL-1 receptor antagonist made it possible to obtain evidence on the necessity of the IL-1 beta binding to the type I IL-1 receptor for the nSMase activation. It appears that the IL-1 beta effects on the CNS are realized via IL-1 receptor type I and activation of the nSMase as an initiating enzyme of the sphingomyelin cascade.

[Effect of modification of the structure of interleukin-1beta on its physiological activity]. / Vliianie modifikatsii struktury interleikina-1beta na ego physiologicheskuiu aktivnost'.

Modification of the structure of recombinant human IL-1 beta: deletion of the amino acids serine, asparagine, and asparagic acid in position 52-54 in mutant delta SND, led to major changes in its functional activity. Significant reduction of the main IL-1 beta activities: concomitant, pyrogenic and corticotropic ones in the mutant delta SND, suggests the latter to be a partial agonist of IL-1 beta. Nevertheless the reduction in certain parameters of the humoral immune response in mice following administration of the delta SND preparation suggests that, when manifesting its immunomodulatory properties, the delta SND acts as a partial antagonist of the IL-1 beta.