Effect of epitalon on interleukin-1beta signal transduction and the reaction of thymocyte blast transformation under stress.
OBJECTIVE
The aim of this research consisted in studying the effects of tetrapeptide Epitalon on both thymocyte proliferation and interleukin-1beta (IL-1beta) signal transduction via sphingomyelin pathway in the cerebral cortex membranes of mice exposed to stresses exerting diverse effects upon humoral immune response.


METHODS
The experiments were performed on male (CBAxC(57)BL(6))F1 mice aged 8 10 weeks. Two models of experimental stress were used: immune-stimulatory rotation stress and immune-suppressive combined stress (cooling followed by immobilization). The concomitant effect of Epitalon was determined according to its influence on thymocyte proliferation stimulated by concanavalin A at a sub-optimal dose and recombinant IL-1beta. The activity of membrane neutral sphingomyelinase (nSMase), the key enzyme of the sphingomyelin signal transduction pathway, was assayed according to modified Rao and Spence's method (1976).


RESULTS
The investigation demonstrated that Epitalon increased thymocyte proliferative activity, both enhanced under rotation stress and suppressed under combined one. It also increased IL-1beta concomitant effect. These findings corresponded to Epitalon effect on diverse stress-induced changes in nSMase activity in cerebral cortex fraction P2. Epitalon activated nSMase in the cerebral cortex membranes of intact mice and increased IL-1beta stimulatory effect on the enzyme activity.


CONCLUSIONS
The obtained results provided a conclusive evidence of Epitalon stress-protective effect at the level of IL-1beta signal transduction via sphingomyelin pathway in the nerve tissue, as well as at the level of target thymocyte proliferation.
Khavinson
Vladimir Kh
VKh
St. Petersburg Institute of Bioregulation and Gerontology, North-Western Branch of the Russian Academy of Medical Sciences, 12 Acad. Pavlov Street, 197376 St. Petersburg, Russia.
Korneva
Elena A
EA
Malinin
Vladimir V
VV
Rybakina
Elena G
EG
Pivanovich
Irina Yu
IY
Shanin
Sergey N
SN
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000737:chemistry / Q000201:enzymology; D002540:Cerebral Cortex / Q000737:chemistry / Q000201:enzymology; D003208:Concanavalin A / Q000494:pharmacology; D003433:Crosses, Genetic; D004789:Enzyme Activation / Q000187:drug effects; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009842:Oligopeptides / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012399:Rotation / Q000009:adverse effects; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology*; D013108:Sphingomyelin Phosphodiesterase / Q000737:chemistry; D013109:Sphingomyelins / Q000378:metabolism; D013312:Stress, Physiological / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D007375:Interleukin-1; D009842:Oligopeptides; D011994:Recombinant Proteins; D013109:Sphingomyelins; D003208:Concanavalin A; D013108:Sphingomyelin Phosphodiesterase; C421253:alanyl-glutamyl-aspartyl-glycine