Excretory/secretory products from plerocercoids of Spirometra erinacei reduce iNOS and chemokine mRNA levels in peritoneal macrophages stimulated with cytokines and/or LPS.
During infection with plerocercoids of Spirometra erinacei, organisms in the peritoneal cavity of infected animals have many bound inflammatory leukocytes yet survive apparently unharmed. Coculture of IFN gamma and LPS stimulated mouse peritoneal macrophages with live plerocercoids suppressed the mRNA expression of the inducible isoform of nitric oxide synthase (iNOS) and JE, the murine homologue of monocyte chemotactic protein-1 (MCP-1). Excretory/secretory (ES) products from plerocercoids also suppressed the induced iNOS and JE mRNA and reduced nitrite production of macrophages in a dose dependent manner. The suppression of inducible mRNA levels in macrophages cultured for 24 h with ES products varied with the nature of the stimuli; IFN gamma/ LPS-induced iNOS mRNA levels were effected less than were iNOS mRNA levels induced by IFN gamma/IL-2 or IFN gamma/ TNF alpha. Similar findings were obtained when nitrite production was measured. Thus modulation of LPS and cytokine inducible mRNA levels appear to be the primary target of ES products. We speculate that a major physiological role for this inhibitory activity in ES products might be the down regulation of pro-inflammatory gene expression.
Fukumoto
S
S
Department of Immunology, Cleveland Clinic Foundation, Ohio 44195, USA.
Hirai
K
K
Tanihata
T
T
Ohmori
Y
Y
Stuehr
D J
DJ
Hamilton
T A
TA
D000818:Animals; D018925:Chemokines / Q000235:genetics*; D016207:Cytokines / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins; D013146:Spirometra / Q000276:immunology*
D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase