Lipophosphoglycan from Leishmania suppresses agonist-induced interleukin 1β gene expression in human monocytes via a unique promoter sequence

摘要: Leishmania are parasites that survive within macrophages by mechanism(s) not entirely known. Depression of cellular immunity and diminished production interleukin 1β (IL-1β) tumor necrosis factor α potential ways which the parasite survives macrophages. We examined lipophosphoglycan (LPG), a major glycolipid Leishmania, perturbs cytokine gene expression. LPG treatment THP-1 monocytes suppressed endotoxin induction IL-1β steady-state mRNA greater than 90%, while having no effect on expression control gene. The addition 2 h before or after challenge significantly 90% 70%, respectively. also inhibited Staphylococcus inhibitory is agonist-specific because did suppress phorbol 12-myristate 13-acetate. A unique DNA sequence located −310 to −57 nucleotide region promoter was found mediate LPG’s activity. requirement for demonstrated abrogation activity truncation deletion sequence. Furthermore, minimal (positions +15) mediated with dose kinetic profiles were similar suppression mRNA. These findings delineated responds act as “gene silencer,” function, our knowledge, previously described. several mediators inflammation persistence significant suggest has therapeutic may be exploited therapy sepsis, acute respiratory distress syndrome, autoimmune diseases.