title: The anacardic 6-pentadecyl salicylic acid induces macrophage activation via the phosphorylation of ERK1/2, JNK, P38 kinases and NF-κB.
abstract: Amphipterygium adstringens is a plant traditionally used to treat gingivitis, gastric ulcer and even gastric cancer but the mechanism involved in the regulation of the immune response is not elucidated yet. The 6-pentadecylsalicylic acid (6SA) is the main anacardic acid found in A. adstringens. In order to evaluate the immune-modulatory abilities of 6SA, we used mouse splenocytes and determined the phosphorylation of the transcription factor NF-κB and MAP kinases ERK1/2, JNK and p38 in helper and cytotoxic T cells, natural killer (NK) cells and F4/80(+) macrophages. Treatment with 6SA was not cytotoxic as measured by both trypan blue exclusion and tetrazolium salts (MTT) tests. Additionally, 6SA did not alter the proportion of helper and cytotoxic T lymphocytes, NK cells or macrophages. Moreover, 6SA treatment significantly increased the phosphorylation of ERK1/2, JNK, P38 and NF-κB mainly in macrophages. In this cells (peritoneal macrophages), treatment with 6SA increased the secretion of nitric oxide (NO), interleukin (IL)-6 and tumour necrosis factor (TNF)-α and decreased the secretion of IL-4 and IL-10 depending on MAPK and NF-κB phosphorylation. In addition, 6SA increased the migration and phagocytic activity of macrophages also depending on the phosphorylation of different kinases. These data suggest that 6SA induces the classical activation pathway in macrophages via the phosphorylation of MAP kinases and NF-κB thus activating the adaptive immune system.
authors.affiliation: Department of Toxicology, Centre for Research and Advanced Studies of the National Polytechnic Institute, Av. IPN, 2508, San Pedro Zacatenco, Mexico City 07360, Mexico.
authors.forename: J N Rashida
authors.initials: JNR
authors.lastname: Gnanaprakasam
authors.affiliation: Department of Toxicology, Centre for Research and Advanced Studies of the National Polytechnic Institute, Av. IPN, 2508, San Pedro Zacatenco, Mexico City 07360, Mexico.
authors.forename: Elizabet
authors.initials: E
authors.lastname: Estrada-Muñiz
authors.affiliation: Department of Toxicology, Centre for Research and Advanced Studies of the National Polytechnic Institute, Av. IPN, 2508, San Pedro Zacatenco, Mexico City 07360, Mexico. Electronic address: lvega@cinvestav.mx.
authors.forename: Libia
authors.initials: L
authors.lastname: Vega
mesh_terms: D048729:Anacardic Acids / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D007155:Immunologic Factors / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism
chemical_list: D048729:Anacardic Acids; D016207:Cytokines; D007155:Immunologic Factors; D016328:NF-kappa B; C088115:anacardic acid; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: 6-pentadecyl salicylic acid; Immuno-modulation; MAP kinases; Macrophages