Lack of IL-1 receptor antagonistic activity of the capsular F1 antigen of Yersinia pestis.
Because capsular F1 antigen of Yersinia pestis is reported to share sequence homology with interleukin-1 receptor antagonist (IL-1ra), we investigated the potential IL-1 receptor antagonistic activity of F1 on human endothelial cells (EC). The biological activities of IL-1 receptor antagonist (IL-1ra) or IL-1ra-like molecule were measured by its ability to suppress the IL-1beta-mediated induction of adhesion molecules (ICAM and ELAM) on EC and of IL-6 secretion by these cells. Two different, purified, immunogenic and biologically active preparations of F1, at concentrations up to 10-fold higher than that of IL-1ra, did not exhibit any inhibitory activities of IL-1ra. These F1 preparations also did not activate peripheral blood mononuclear cells to produce IL-4 or IL-10, cytokines which might downregulate pro-inflammatory cytokine production in response to infection. Thus, even though there is a high degree of similarity between F1 antigen and IL-1ra in three-dimensional structure by computer modeling and sequence homology, our work indicates that F1 antigen of Y. pestis does not have IL-1ra-like activity.
Krakauer
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T
Department of Immunology and Molecular Biology, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
Heath
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D
D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism*; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D015010:Yersinia pestis
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D019040:E-Selectin; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; C086725:caf1 protein, Yersinia pestis; D018799:Intercellular Adhesion Molecule-1