In vitro anti-inflammatory activity of Phlebodium decumanum. Modulation of tumor necrosis factor and soluble TNF receptors.
The immunomodulatory activity of a standardized water soluble fraction of the fern Phlebodium decumanum (EXPLY-37) previously shown to have "in vivo" anti-inflammatory activity was analyzed "in vitro". This extract inhibited tumor necrosis factor (TNF) production by macrophages activated with lipopolysaccharide (LPS) or LPS plus interferon (IFN)-gamma. In contrast, nitric oxide (NO) and interleukin (IL)-1beta production were not affected in the same cultures, whereas IL-6 production was partially inhibited. More interestingly, EXPLY-37 increased the release of soluble TNF-receptor 2 (sTNFR2) and of IL-1R antagonist (IL-1Ra) but not of sTNFR1, by activated macrophages. EXPLY-37 had no effect on T lymphocyte activation, measured as proliferation as well as expression of early and late cell surface antigens CD69, CD25 (IL-2R-alpha) and CD71 (transferrin receptor) at the cell membrane. At the molecular level, EXPLY-37 did not inhibit the activation of the nuclear factor kappa B (NF-kappaB) transcription factor by TNF. In summary, EXPLY-37 has two anti-inflammatory activities "in vitro": it decreases TNF production and increases IL-1Ra and sTNFR2, which may be able to neutralize IL-1 and TNF activity, respectively.
Punzón
Carmen
C
Centro de Biología Molecular "Severo Ochoa", CSIC-UAM Universidad Autónoma de Madrid, Canto Blanco, E-28049 Madrid, Spain.
Alcaide
Antonio
A
Fresno
Manuel
M
D000276:Adjuvants, Immunologic / Q000302:isolation & purification / Q000494:pharmacology*; D000328:Adult; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology*; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D029621:Polypodiaceae / Q000737:chemistry*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000235:genetics; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; C484878:EXPLY 37; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha