Cocoa Flavonols and Procyanidins Promote Transforming Growth Factor-β1 Homeostasis in Peripheral Blood Mononuclear Cells1

2003 ◽  
Vol 228 (1) ◽  
pp. 93-99 ◽  
Author(s):  
T.K. Mao ◽  
J. Van De Water ◽  
C.L. Keen ◽  
H.H. Schmitz ◽  
M.E. Gershwin

Evidence suggests that certain flavan-3-ols and procyanidins (FP) can have a positive influence on cardiovascular health. It has been previously reported that FP isolated from cocoa can potentially modulate the level and production of several signaling molecules associated with immune function and inflammation, including several cytokines and eicosanoids. In the present study, we examined whether FP fractions monomers through decamers modulate secretion of the cytokine transforming growth factor (TGF)-β1 from resting human peripheral blood mononuclear cells (PBMC). A total of 13 healthy subjects were studied and grouped according to their baseline production of TGF-β1. When cells from individuals with low baseline levels of TGF-β1 (n = 7) were stimulated by individual FP fractions (25 μg/ml), TGF-β1 release was enhanced in the range of 15%–66% over baseline (P < 0.05; monomer, dimer, and tetramer). The low-molecular-weight FP fractions (≤pentamer) were more effective at augmenting TGF-β1 secretion than their larger counterparts (≥hexamer), with the monomer and dimer inducing the greatest increases (66% and 68%, respectively). In contrast to the above, TGF-β1 secretion from high TGF-β1 baseline subjects (n = 6) was inhibited by individual FP fractions (P < 0.05; trimer through decamer). The inhibition was most pronounced with trimeric through decameric fractions (28%–42%), and monomers and dimers moderately inhibited TGF-β1 release (17% and 23%, respectively). Given the vascular actions associated with TGF-β1, we suggest that in healthy individuals, homeostatic modulation of its production by FP offers an additional mechanism by which FP-rich foods can potentially benefit cardiovascular health.

2020 ◽  
Vol 318 (1) ◽  
pp. L165-L179 ◽  
Author(s):  
Tejas R. Karhadkar ◽  
Wensheng Chen ◽  
Richard H. Gomer

Pulmonary fibrosis involves the formation of inappropriate scar tissue in the lungs, but what drives fibrosis is unclear. Sialidases (also called neuraminidases) cleave terminal sialic acids from glycoconjugates. In humans and mice, pulmonary fibrosis is associated with desialylation of glycoconjugates and upregulation of sialidases. Of the four mammalian sialidases, we previously detected only NEU3 in the bronchoalveolar lavage fluid from mice with bleomycin-induced pulmonary fibrosis. In this report, we show that NEU3 upregulates extracellular accumulation of the profibrotic cytokines IL-6 and IL-1β, and IL-6 upregulates NEU3 in human peripheral blood mononuclear cells, suggesting that NEU3 may be part of a positive feedback loop potentiating fibrosis. To further elucidate the role of NEU3 in fibrosis, we used bleomycin to induce lung fibrosis in wild-type C57BL/6 and Neu3−/− mice. At 21 days after bleomycin, compared with male and female C57BL/6 mice, male and female Neu3−/− mice had significantly less inflammation, less upregulation of other sialidases and the profibrotic cytokine active transforming growth factor β1, and less fibrosis in the lungs. Our results suggest that NEU3 participates in fibrosis and that NEU3 could be a target to develop treatments for fibrosis.


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