scholarly journals Lactosylceramide Is Essential for the Osteoclastogenesis Mediated by Macrophage-Colony-stimulating Factor and Receptor Activator of Nuclear Factor-κB Ligand

2001 ◽  
Vol 276 (49) ◽  
pp. 46031-46038 ◽  
Author(s):  
Tsutomu Iwamoto ◽  
Satoshi Fukumoto ◽  
Kazuhiro Kanaoka ◽  
Eiko Sakai ◽  
Mitsue Shibata ◽  
...  
Keyword(s):  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Colony Stimulating Factor ◽  
Receptor Activator ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Inhibitor of nuclear factor-κB induction by cAMP antagonizes interleukin-1-induced human macrophage-colony-stimulating-factor expression

2001 ◽  
Vol 356 (2) ◽  
pp. 525-530 ◽  
Author(s):  
Pisate J. KAMTHONG ◽  
Ming-chi WU
Keyword(s):  
Nuclear Factor Κb ◽  
Human Macrophage ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Colony Stimulating Factor ◽  
Dibutyryl Camp ◽  
Iκb Kinase ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

We have recently reported that interleukin-1α (IL-1α) can induce human macrophage colony-stimulating factor (M-CSF) expression through nuclear factor κB (NF-κB) activation, and treatment of human pancreatic MIA PaCa-2 cancer cells with forskolin or cAMP attenuated the NF-κB activation as well as M-CSF expression. In this study, we have further investigated the mechanism of cAMP attenuation. MIA PaCa-2 cells were incubated with forskolin or dibutyryl-cAMP and then stimulated with IL-1 for 1h. Cell lysates were immunoprecipitated by anti-inhibitory κB (IκB) kinase-β (IKKβ) antibody and the immune complex assayed for kinase activity using recombinant inhibitor of NF-κB (IκBα) as substrate. The levels of IKKβ in the respective cellular proteins were measured by subsequent Western blot. The results show that the level of IKK protein remains constant in the presence of cAMP, forskolin and/or IL-1, whereas IKK activity was robustly stimulated by IL-1. Nonetheless, dibutyryl-cAMP or forskolin did not affect the IKK activation induced by IL-1. This experiment suggests that elevated cAMP has no effect on IKK activity. IκBα protein level decreased markedly in IL-1-treated cells compared with the untreated. By contrast, cells treated with cAMP or forskolin possessed discernibly higher IκBα levels. In addition, we observed that forskolin potentiated and prolonged the IL-1-induced IκBα mRNA levels, whereas it did not stabilize the IκBα mRNA message. Wholly, these studies indicate that elevated cAMP antagonizes IL-1-induced M-CSF transcription by up-regulating IκBα gene induction and its consequent attenuation of NF-κB activation.

scholarly journals Efficiency of Estrogen Replacement Therapy in Osteoporosis

2018 ◽  
Vol 3 (3) ◽  
pp. 134
Author(s):  
Syed Mohammad Mazhar Uddin ◽  
Aatera Haq ◽  
Haris Sheikh ◽  
Uzair Yaqoob ◽  
Bushra Zafar Sayeed
Keyword(s):  
Nuclear Factor Kappa B ◽  
Calcium Absorption ◽  
Estrogen Therapy ◽  
Nuclear Factor ◽  
Colony Stimulating Factor ◽  
Nuclear Factor Kappa ◽  
Receptor Activator ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Estrogen therapy has been taken as a settled approach for both prevention and treatment of osteoporosis, especially in post-menopausal women as well as for the treatment of symptoms associated with menopause. Recent studies suggest that nuclear factor kappa-B ligand/receptor activator of nuclear factor kappa-B/osteoprotegerin system plays a signi cant role in osteoclastic activity regulation, with receptor activator of nuclear factor kappa-B ligand signaling in the presence of macrophage colony stimulating factor leading to increase in osteoclastic differentiation and functioning while osteoprotegerin neutralizing receptor activator of nuclear factor kappa-B ligand. Estrogen acts by increasing osteoprotegerin levels, and decreasing macrophage colony stimulating factor and receptor activator of nuclear factor kappa-B, thereby reducing bone resorption. Furthermore, estrogen is also known to be causing increased calcium absorption through gut and kidneys. The use of estrogen therapy in patients of osteoporosis is also considered to be highly cost effective. On the negative side, studies have shown that oral estrogen therapy can lead to complications like cholelithiasis, thrombophlebitis and pulmonary embolism, the most detrimental being endometrial cancer. But studies have shown that it can be virtually eliminated with the addition of progesterone in the cyclic combined regimen. Majority of bene cial effects occur with long term use of estrogen therapy, but the compliance by most of women appears to be poor and is usually due to lack of awareness, misconceptions, advice of physician and phobia of side effects. Additional studies should therefore be conducted to evaluate in detail the causes of non-compliance and strategies to improve compliance. The bene t of quality of life improvement with estrogen therapy should be taken into account and further evaluated via studies.

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