Article Publish Status: FREE
Abstract 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 Source:

J Cell Mol Med. 2015 Jul ;19(7):1548-56. Epub 2015 Mar 21. PMID: 25807993

Abstract Author(s):

Mirko Pesce, Sara Franceschelli, Alessio Ferrone, Maria Anna De Lutiis, Antonia Patruno, Alfredo Grilli, Mario Felaco, Lorenza Speranza

Article Affiliation:

Mirko Pesce


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 factorβ-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 dataconfirm 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.

Study Type : In Vitro Study

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