Regulation of TNF-α, IL-1β and ICAM-1 Gene Expression in THP-1 Monocytes Stimulated with Plasmodium falciparum-Cultured Medium by Excretory/Secretory Products from Spirometra erinaceieuropaei Plerocercoids

We have reported that excretory/secretory (ES) products from Spirometra erinaceieuropaei plerocercoids suppress production and gene expression of tumor necrosis factor (TNF)-α in murine macrophages stimulated with lipopolysaccharide. The present study demonstrates that ES products suppress TNF-α, interleukin (IL)-1β and intercellular adhesion molecule (ICAM)-1 gene expression in human monocytic leukemia cell line THP-1 stimulated with Plasmodium falciparum-cultured medium (Pf-CM). Inhibition of extracellular-signal regulated protein kinase 1/2 (ERK1/2) with PD98059 reduced TNF-α, IL-1β and ICAM-1 gene expression; on the contrary inhibition of p38 mitogen-activated protein kinase (MAPK) with SB203580 increased the expression of these genes. These findings indicated that ERK1/2, but not p38 MAPK pathway is important for induction of TNF-α, IL-1β and ICAM-1 gene expression in Pf-CM stimulated THP-1 monocytes. ES products additionally suppress IL-1β, but not TNF-α and ICAM-1 gene expression in Pf-CM stimulated THP-1 cells treated with PD98059. We hypothesize that ES products may be useful in reducing falciparum malaria-induced inflammatory response and sequestration in the late stage of malarial diseases such as cerebral malaria.