scholarly journals Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-α

2000 ◽  
Vol 106 (10) ◽  
pp. 1229-1237 ◽  
Author(s):  
Simone Cenci ◽  
M. Neale Weitzmann ◽  
Cristiana Roggia ◽  
Noriyuki Namba ◽  
Deborah Novack ◽  
...  
Keyword(s):  
T Cell ◽  
Bone Loss ◽  
Estrogen Deficiency ◽  
Cell Production ◽  
Tnf Α

scholarly journals An IL-7-dependent rebound in thymic T cell output contributes to the bone loss induced by estrogen deficiency

2005 ◽  
Vol 102 (46) ◽  
pp. 16735-16740 ◽  
Author(s):  
M. R. Ryan ◽  
R. Shepherd ◽  
J. K. Leavey ◽  
Y. Gao ◽  
F. Grassi ◽  
...  
Keyword(s):  
T Cell ◽  
Bone Loss ◽  
Estrogen Deficiency

scholarly journals The Role of Interleukin-10 (IL-10) in IL-15–Mediated T-Cell Responses

Blood ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4513-4521 ◽  
Author(s):  
Dieter Körholz ◽  
Ursula Banning ◽  
Halvard Bönig ◽  
Markus Grewe ◽  
Marion Schneider ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Interleukin 10 ◽  
T Cell Proliferation ◽  
Cell Production ◽  
Cd25 Expression ◽  
Tnf Α ◽  
Ifn Γ

Abstract Interleukin-15 (IL-15) is a potent T-cell stimulating factor, which has recently been used for pre-clinical in vivo immunotherapy. Here, the IL-15 effect on CD3-stimulated peripheral human T cells was investigated. IL-15 induced a significant T-cell proliferation and upregulated CD25 expression. IL-15 significantly enhanced T-cell production of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and IL-10. Between 10- and 100-fold greater concentrations of IL-15 were necessary to reach a biological effect equivalent to that of IL-2. Blockade of IL-2 binding to the high-affinity IL-2 receptor did not affect the IL-15 effects, suggesting that IL-15 did not act by inducing endogenous IL-2. Exogenously administered IL-10 significantly reduced the IL-15 and IL-2–mediated IFN-γ and TNF-α production, whereas T-cell proliferation and CD25 expression were not affected. The inhibitory effects of exogenously administered IL-10 on T-cell cytokine production appeared indirect, and are likely secondary to decreased IL-12 production by accessory cells. Inhibition of endogenous IL-10 binding to the IL-10 receptor significantly increased IFN-γ and TNF-α release from T cells. These data suggest that endogenous IL-10 can regulate activated T-cell production of IFN-γ and TNF-α via a paracrine negative feedback loop. The observations of this study could be of relevance for the therapeutic use of IL-15 in vivo.

scholarly journals Estrogen Deficiency Exacerbates Type 1 Diabetes–Induced Bone TNF-α Expression and Osteoporosis in Female Mice

Endocrinology ◽  
2017 ◽  
Vol 158 (7) ◽  
pp. 2086-2101 ◽  
Author(s):  
Sandi Raehtz ◽  
Hayley Bierhalter ◽  
Daniel Schoenherr ◽  
Narayanan Parameswaran ◽  
Laura R. McCabe
Keyword(s):  
Type 1 Diabetes ◽  
Bone Loss ◽  
Fracture Risk ◽  
Volume Fraction ◽  
Estrogen Deficiency ◽  
Bone Volume Fraction ◽  
Number Of Patients ◽  
Tnf Α

Abstract Estrogen deficiency after menopause is associated with rapid bone loss, osteoporosis, and increased fracture risk. Type 1 diabetes (T1D), characterized by hypoinsulinemia and hyperglycemia, is also associated with bone loss and increased fracture risk. With better treatment options, T1D patients are living longer; therefore, the number of patients having both T1D and estrogen deficiency is increasing. Little is known about the mechanistic impact of T1D in conjunction with estrogen deficiency on bone physiology and density. To investigate this, 11-week-old mice were ovariectomized (OVX), and T1D was induced by multiple low-dose streptozotocin injection. Microcomputed tomographic analysis indicated a marked reduction in trabecular bone volume fraction (BVF) in T1D-OVX mice (~82%) that was far greater than the reductions (~50%) in BVF in either the OVX and T1D groups. Osteoblast markers, number, and activity were significantly decreased in T1D-OVX mice, to a greater extent than either T1D or OVX mice. Correspondingly, marrow adiposity was significantly increased in T1D-OVX mouse bone. Bone expression analyses revealed that tumor necrosis factor (TNF)–α levels were highest in T1D-OVX mice and correlated with bone loss, and osteoblast and osteocyte death. In vitro studies indicate that estrogen deficiency and high glucose enhance TNF-α expression in response to inflammatory signals. Taken together, T1D combined with estrogen deficiency has a major effect on bone inflammation, which contributes to suppressed bone formation and osteoporosis. Understanding the mechanisms/effects of estrogen deficiency in the presence of T1D on bone health is essential for fracture prevention in this patient population.

scholarly journals Anti IL-17A therapy inhibits bone loss in TNF-α-mediated murine arthritis by modulation of the T-cell balance

2011 ◽  
Vol 42 (2) ◽  
pp. 413-423 ◽  
Author(s):  
Karin Zwerina ◽  
Marije Koenders ◽  
Axel Hueber ◽  
Renoud J. Marijnissen ◽  
Wolfgang Baum ◽  
...  
Keyword(s):  
T Cell ◽  
Bone Loss ◽  
Tnf Α ◽  
Cell Balance

scholarly journals The Role of Interleukin-10 (IL-10) in IL-15–Mediated T-Cell Responses

Blood ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4513-4521
Author(s):  
Dieter Körholz ◽  
Ursula Banning ◽  
Halvard Bönig ◽  
Markus Grewe ◽  
Marion Schneider ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Interleukin 10 ◽  
T Cell Proliferation ◽  
Cell Production ◽  
Cd25 Expression ◽  
Tnf Α ◽  
Ifn Γ

Interleukin-15 (IL-15) is a potent T-cell stimulating factor, which has recently been used for pre-clinical in vivo immunotherapy. Here, the IL-15 effect on CD3-stimulated peripheral human T cells was investigated. IL-15 induced a significant T-cell proliferation and upregulated CD25 expression. IL-15 significantly enhanced T-cell production of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and IL-10. Between 10- and 100-fold greater concentrations of IL-15 were necessary to reach a biological effect equivalent to that of IL-2. Blockade of IL-2 binding to the high-affinity IL-2 receptor did not affect the IL-15 effects, suggesting that IL-15 did not act by inducing endogenous IL-2. Exogenously administered IL-10 significantly reduced the IL-15 and IL-2–mediated IFN-γ and TNF-α production, whereas T-cell proliferation and CD25 expression were not affected. The inhibitory effects of exogenously administered IL-10 on T-cell cytokine production appeared indirect, and are likely secondary to decreased IL-12 production by accessory cells. Inhibition of endogenous IL-10 binding to the IL-10 receptor significantly increased IFN-γ and TNF-α release from T cells. These data suggest that endogenous IL-10 can regulate activated T-cell production of IFN-γ and TNF-α via a paracrine negative feedback loop. The observations of this study could be of relevance for the therapeutic use of IL-15 in vivo.

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