title: Verbascoside down-regulates some pro-inflammatory signal transduction pathways by increasing the activity of tyrosine phosphatase SHP-1 in the U937 cell line.
abstract: Polyphenols are the major components of many traditional herbal remedies, which exhibit several beneficial effects including anti-inflammation and antioxidant properties. Src homology region 2 domain-containing phosphatase-1 (SHP-1) is a redox sensitive protein tyrosine phosphatase that negatively influences downstream signalling molecules, such as mitogen-activated protein kinases, thereby inhibiting inflammatory signalling induced by lipopolysaccharide (LPS). Because a role of transforming growth factor β-activated kinase-1 (TAK1) in the upstream regulation of JNK molecule has been well demonstrated, we conjectured that SHP-1 could mediate the anti-inflammatory effect of verbascoside through the regulation of TAK-1/JNK/AP-1 signalling in the U937 cell line. Our results demonstrate that verbascoside increased the phosphorylation of SHP-1, by attenuating the activation of TAK-1/JNK/AP-1 signalling. This leads to a reduction in the expression and activity of both COX and NOS. Moreover, SHP-1 depletion deletes verbascoside inhibitory effects on pro-inflammatory molecules induced by LPS. Our data confirm that SHP-1 plays a critical role in restoring the physiological mechanisms of inducible proteins such as COX2 and iNOS, and that the down-regulation of TAK-1/JNK/AP-1 signalling by targeting SHP-1 should be considered as a new therapeutic strategy for the treatment of inflammatory diseases.
authors: Department of Psychological, Humanistic and Territorial Sciences, University G. D'Annunzio, Chieti, Italy.
authors: Mirko
authors: M
authors: Pesce
authors: Department of Medicine and Science of Aging, University G. D'Annunzio, Chieti, Italy.
authors: Sara
authors: S
authors: Franceschelli
authors: Department of Medicine and Science of Aging, University G. D'Annunzio, Chieti, Italy.
authors: Alessio
authors: A
authors: Ferrone
authors: Department of Medicine and Science of Aging, University G. D'Annunzio, Chieti, Italy.
authors: Maria Anna
authors: MA
authors: De Lutiis
authors: Department of Medicine and Science of Aging, University G. D'Annunzio, Chieti, Italy.
authors: Antonia
authors: A
authors: Patruno
authors: Department of Psychological, Humanistic and Territorial Sciences, University G. D'Annunzio, Chieti, Italy.
authors: Alfredo
authors: A
authors: Grilli
authors: Department of Medicine and Science of Aging, University G. D'Annunzio, Chieti, Italy.
authors: Mario
authors: M
authors: Felaco
authors: Department of Medicine and Science of Aging, University G. D'Annunzio, Chieti, Italy.
authors: Lorenza
authors: L
authors: Speranza
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000201:enzymology* / Q000473:pathology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D020298:U937 Cells; D000099151:MAP Kinase Kinase Kinase 7; D059808:Polyphenols
chemical_list: D051546:Cyclooxygenase 2; D005960:Glucosides; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D052247:Nitric Oxide Synthase Type II; D010636:Phenols; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D018808:Transcription Factor AP-1; D014443:Tyrosine; D000099151:MAP Kinase Kinase Kinase 7; C058956:acteoside; D059808:Polyphenols
keywords: COX 2; SHP-1; Tak-1; iNOS; verbascoside