[Effect of Yersinia pestis EV 76 lypopolysaccharides with different levels of toxicity on dynamics of TNF-alpha and INF-gamma synthesis by human monocytes].
AIM. To study dynamics of synthesis of TNF-alpha and INF-gamma by cell line U-937 human monocytes under the effect of Yersinia pestis EV 76 lypopolysaccharides (LPS) with different levels of toxicity: original LPS28 and LPS37 as well as their conformationally--changed variants with enhanced toxicity--complex of LPS with murine toxin (MT) of Y. pestis, and LPS modified by biologicall active compound (BAC) obtained from human erythrocytes.


METHODS
Using phenol method, LPS were obtained from Y. pestis EV 76 cells grown at 28 and 37 degrees C. Production of cytokines was measured by ELISA.


RESULTS
It was shown that original and modified forms of LPS28 and LPS37 induce synthesis of both TNF-alpha and INF-gamma by human monocytes. Expression of genes for two ways of synthesis of these cytokines points to activation and transmission of signal induced by all studied forms of Y. pestis EV 76 LPS through TLR4. Levels of activity of MyD88-dependent and MyD88-independent signaling pathways are different and depend from chemical structure of LPS28 and LPS37, conformation of their modified forms and duration of their exposition with monocytes. Dynamics ofcytokine synthesis corresponds to response of synergized TLR on activation with profound agonistic/antagonistic effect.


CONCLUSIONS
It was determined that conformational modifications of Y. pestis EV76 LPS occurring due to effect of MT and BAC accompanied by quantitative, qualitative and temporal changes of TNF-alpha and INF-gamma synthesis by human monocytes and correlate with increase of their toxic properties.
Sokolova
E P
EP
Demidova
G V
GV
Ziuzina
V P
VP
Alekseeva
L P
LP
Bespalova
I A
IA
Tynianova
V I
VI
D000818:Animals; D001685:Biological Factors / Q000494:pharmacology; D002478:Cells, Cultured; D004912:Erythrocytes / Q000737:chemistry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology* / Q000633:toxicity; D051379:Mice; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D015398:Signal Transduction; D013696:Temperature; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015010:Yersinia pestis / Q000254:growth & development / Q000276:immunology*
D001685:Biological Factors; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma