title: β-Sitosterol down-regulates some pro-inflammatory signal transduction pathways by increasing the activity of tyrosine phosphatase SHP-1 in J774A.1 murine macrophages.
abstract: The objective of the present study was to examine the anti-inflammatory effects of β-sitosterol (SIT), the most common phytosterol in the diet, and to investigate its involvement in NF-κB and STAT1 pathways as potential mechanisms. In addition, the activity of the phosphatase SHP-1 as a negative modulator to these pathways, was investigated. Utilizing murine J774A.1 macrophages, cells were treated with various physiological concentrations of SIT and stimulated with LPS (100 ng/ml) for 6h. Results indicate that 1 and 16 μM SITs increased SHP-1 activity by 300% and 200%, respectively. Similar results were obtained using western blot analysis. Additionally, we observed reductions in the release of some pro-inflammatory cytokines and chemokines as well as an increase in anti-inflammatory IL-10 with SIT treatments. The results also demonstrate the inhibition of STAT1 with SIT treatment. Moreover, translocation of NF-κB to the nucleus was inhibited with SIT as indicated by decreased phosphorylation and the use of ImageStream cytometry. In conclusion, the present study demonstrates the anti-inflammatory effect on macrophages by inactivating STAT1 and NF-κB, which could be mediated by the activation of SHP-1.
authors.affiliation: Department of Exercise and Nutrition Sciences, University at Buffalo, Buffalo, NY 14214, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Valerio
authors.forename: Atif B
authors.initials: AB
authors.lastname: Awad
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D012855:Sitosterols / Q000494:pharmacology*
chemical_list: D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; D012855:Sitosterols; C494080:Stat1 protein, mouse; D016753:Interleukin-10; C025473:gamma-sitosterol; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6