Regulation of interleukin-2 and interleukin-6 production from T-cells: Involvement of interleukin-1 β and transforming growth factor-β

1990 ◽  
Vol 126 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Terje Espevik ◽  
Anders Waage ◽  
Arild Faxvaag ◽  
M.Refaat Shalaby
2019 ◽  
Vol 47 (8) ◽  
pp. 1955-1963 ◽  
Author(s):  
Sean M. Muir ◽  
Natalie Reisbig ◽  
Michael Baria ◽  
Christopher Kaeding ◽  
Alicia L. Bertone

Background: Currently, platelet-poor plasma (PPP) is a discarded waste product of platelet-rich plasma (PRP) and may contain valuable proteins. Purpose/Hypothesis: The study’s goal was to evaluate the concentration of plasma as a potential additive biotherapy for the treatment of osteoarthritis. We hypothesized that a novel polyacrylamide concentration device would efficiently concentrate insulin-like growth factor–1 (IGF-1) from PPP and be additive to PRP or autologous protein solution (APS). Study Design: Descriptive laboratory study. Methods: A laboratory study was conducted with human and equine whole blood from healthy volunteers/donors. Fresh samples of blood and plasma were processed and characterized for platelet, white blood cell, and growth factor/cytokine content and then quantified by enzyme-linked immunosorbent assays specific for IGF-1, transforming growth factor–β, interleukin-1β, and interleukin-1 receptor antagonist as representatives of cartilage anabolic and inflammatory mediators. Results: A potent cartilage anabolic protein, IGF-1, was significantly concentrated by the polyacrylamide concentration device in both human and equine PPP. The polyacrylamide device also substantially increased plasma proteins over whole blood, most dramatically key proteins relevant to the treatment of osteoarthritis, including transforming growth factor–β (29-fold over blood) and interleukin-1 receptor antagonist (70-fold over plasma). Conclusion: Concentrated PPP is a unique source for biologically relevant concentrations of IGF-1. PRP and APS can produce greater concentrations of other anabolic and anti-inflammatory proteins not found in plasma. Clinical Relevance: The polyacrylamide device efficiently concentrated PPP to create a unique source of IGF-1 that may supplement orthopaedic biologic therapies.


Blood ◽  
2010 ◽  
Vol 115 (23) ◽  
pp. 4750-4757 ◽  
Author(s):  
Pedro J. Cejas ◽  
Matthew C. Walsh ◽  
Erika L. Pearce ◽  
Daehee Han ◽  
Gretchen M. Harms ◽  
...  

Abstract Transforming growth factor-β (TGF-β) has an essential role in the generation of inducible regulatory T (iTreg) and T helper 17 (Th17) cells. However, little is known about the TGF-β–triggered pathways that drive the early differentiation of these cell populations. Here, we report that CD4+ T cells lacking the molecular adaptor tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) exhibit a specific increase in Th17 differentiation in vivo and in vitro. We show that TRAF6 deficiency renders T cells more sensitive to TGF-β–induced Smad2/3 activation and proliferation arrest. Consistent with this, in TRAF6-deficient T cells, TGF-β more effectively down-regulates interleukin-2 (IL-2), a known inhibitor of Th17 differentiation. Remarkably, TRAF6-deficient cells generate normal numbers of Foxp3-expressing cells in iTreg differentiation conditions where exogenous IL-2 is supplied. These findings show an unexpected role for the adaptor molecule TRAF6 in Smad-mediated TGF-β signaling and Th17 differentiation. Importantly, the data also suggest that a main function of TGF-β in early Th17 differentiation may be the inhibition of autocrine and paracrine IL-2–mediated suppression of Th17 cell generation.


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