Gene expression profiles of inducible nitric oxide synthase and cytokines in Leishmania major-infected macrophage-like RAW 264.7 cells treated with gallic acid.
The effects of gallic acid on the gene expressions of inducible nitric oxide synthase (iNOS) and the cytokines interleukin (IL)-1, IL-10, IL-12, IL-18, TNF-alpha, and interferon (IFN)-gamma were investigated by reverse-transcription polymerase chain reaction (RT-PCR). The experiments were performed in parallel in non-infected and in L. major-infected RAW 264.7 cells and the expression profiles were compared with those mediated by IFN-gamma plus lipopolysaccharide (LPS). The infection per se induced the expression first of IL-1 and TNF-alpha mRNA, later that of IL-10 mRNA. Gallic acid induced low and transient levels of TNF-alpha and IL-10 in non-infected cells, and it clearly enhanced and prolonged iNOS and cytokine mRNA expressions in Leishmania-parasitised cells. Interestingly, and in contrast to activation by IFN-gamma/LPS, gallic acid also stimulated Leishmania-infected cells to produce IFN-gamma mRNA. For IFN-alpha, a sandwich immunoassay was performed to determine its amount present in the supernatant of gallic acid-stimulated RAW 264.7 cells. In showing predominant stimulation of infected cells and the induction especially of IFN-gamma, a cytokine that plays a central role in antimicrobial macrophage and T cell regulation, these data provide the basis for an immunological concept of gallic acid and possibly other plant polyphenols for their beneficial effects in various infectious conditions.
Radtke
Oliver A
OA
Institut für Pharmazeutische Biologie, Freie Universität Berlin, Berlin, Germany.
Kiderlen
Albrecht F
AF
Kayser
Oliver
O
Kolodziej
Herbert
H
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D017931:DNA Primers; D005707:Gallic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation; D007118:Immunoassay; D018320:Leishmania major; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D008517:Phytotherapy; D010946:Plants, Medicinal; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis
D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger; D005707:Gallic Acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse