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Endocrine Reviews 20 (4): 435-459
Copyright © 1999 by The Endocrine Society

Molecular Control of Immune/Inflammatory Responses: Interactions Between Nuclear Factor-{kappa}B and Steroid Receptor-Signaling Pathways

Lorraine I. McKay and John A. Cidlowski

Laboratory of Signal Transduction, Molecular Endocrinology Group, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709

I. Introduction
II. Nuclear Factor-{kappa}B (NF-{kappa}B)
A. Introduction
B. NF-{kappa}B is a dimeric transcription factor
C. The regulatory subunit I{kappa}B is an inhibitor of NF-{kappa}B
D. Activation and function of NF-{kappa}B
E. The transcription factor NF-{kappa}B interacts with multiple transcription factors and transcriptional co-factors
F. Transgenic animals suggest a complex role for NF-{kappa}B family members in immunity and development
III. Steroid Hormones/Receptors: Glucocorticoids and the Glucocorticoid Receptor (GR)
A. General background
B. Glucocorticoid mechanism of action: the GR
C. Glucocorticoid physiology
D. GR/NF-{kappa}B interactions
E. GR interacts with other transcription factors and transcriptional cofactors
IV. NF-{kappa}B and GR Antagonism: Physiological Significance?
V. Interactions Between NF-{kappa}B and Other Steroid Hormone Receptors
A. Androgen receptor (AR)
B. Estrogen receptor (ER)
C. Progesterone receptor (PR)
VI. Summary/Conclusions




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Y. Iwasaki, M. Asai, M. Yoshida, T. Nigawara, M. Kambayashi, and N. Nakashima
Dehydroepiandrosterone-Sulfate Inhibits Nuclear Factor-{kappa}B-Dependent Transcription in Hepatocytes, Possibly through Antioxidant Effect
J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3449 - 3454.
[Abstract] [Full Text] [PDF]

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 J. Pharmacol. Exp. Ther.Home page
C. S. Park, H. Lim, K. J. Han, S. H. Baek, H. O. Sohn, D. W. Lee, Y.-G. Kim, H.-Y. Yun, K. J. Baek, and N. S. Kwon
Inhibition of Nitric Oxide Generation by 23,24-Dihydrocucurbitacin D in Mouse Peritoneal Macrophages
J. Pharmacol. Exp. Ther., May 1, 2004; 309(2): 705 - 710.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
M. A. Iannone, C. A. Simmons, S. H. Kadwell, D. L. Svoboda, D. E. Vanderwall, S.-J. Deng, T. G. Consler, J. Shearin, J. G. Gray, and K. H. Pearce
Correlation between in Vitro Peptide Binding Profiles and Cellular Activities for Estrogen Receptor-Modulating Compounds
Mol. Endocrinol., May 1, 2004; 18(5): 1064 - 1081.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
G. Wu, P. Brouckaert, and T. Olivecrona
Rapid downregulation of adipose tissue lipoprotein lipase activity on food deprivation: evidence that TNF-{alpha} is involved
Am J Physiol Endocrinol Metab, May 1, 2004; 286(5): E711 - E717.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
J. A. Ospina, H. N. Brevig, D. N. Krause, and S. P. Duckles
Estrogen suppresses IL-1{beta}-mediated induction of COX-2 pathway in rat cerebral blood vessels
Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H2010 - H2019.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
C. Y. Hong, J. H. Park, R. S. Ahn, S. Y. Im, H.-S. Choi, J. Soh, S. H. Mellon, and K. Lee
Molecular Mechanism of Suppression of Testicular Steroidogenesis by Proinflammatory Cytokine Tumor Necrosis Factor Alpha
Mol. Cell. Biol., April 1, 2004; 24(7): 2593 - 2604.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
M. U. De Martino, N. Bhattachryya, S. Alesci, T. Ichijo, G. P. Chrousos, and T. Kino
The Glucocorticoid Receptor and the Orphan Nuclear Receptor Chicken Ovalbumin Upstream Promoter-Transcription Factor II Interact with and Mutually Affect Each Other's Transcriptional Activities: Implications for Intermediary Metabolism
Mol. Endocrinol., April 1, 2004; 18(4): 820 - 833.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
C.-d. Geng and W. V. Vedeckis
Steroid-Responsive Sequences in the Human Glucocorticoid Receptor Gene 1A Promoter
Mol. Endocrinol., April 1, 2004; 18(4): 912 - 924.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
H. Leis, A. Page, A. Ramirez, A. Bravo, C. Segrelles, J. Paramio, D. Barettino, J. L. Jorcano, and P. Perez
Glucocorticoid Receptor Counteracts Tumorigenic Activity of Akt in Skin through Interference with the Phosphatidylinositol 3-Kinase Signaling Pathway
Mol. Endocrinol., February 1, 2004; 18(2): 303 - 311.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
J. Wu, Y. Li, J. Dietz, and D. S. Lala
Repression of p65 Transcriptional Activation by the Glucocorticoid Receptor in the Absence of Receptor-Coactivator Interactions
Mol. Endocrinol., January 1, 2004; 18(1): 53 - 62.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
K. Sun and L. Myatt
Enhancement of Glucocorticoid-Induced 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Expression by Proinflammatory Cytokines in Cultured Human Amnion Fibroblasts
Endocrinology, December 1, 2003; 144(12): 5568 - 5577.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
Z. Strakova, M. Szmidt, S. Srisuparp, and A. T. Fazleabas
Inhibition of Matrix Metalloproteinases Prevents the Synthesis of Insulin-Like Growth Factor Binding Protein-1 during Decidualization in the Baboon
Endocrinology, December 1, 2003; 144(12): 5339 - 5346.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. Takuma, T. Kaneda, T. Sato, S. Ninomiya, M. Kumegawa, and Y. Hakeda
Dexamethasone Enhances Osteoclast Formation Synergistically with Transforming Growth Factor-{beta} by Stimulating the Priming of Osteoclast Progenitors for Differentiation into Osteoclasts
J. Biol. Chem., November 7, 2003; 278(45): 44667 - 44674.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
S. Altuwaijri, H.-K. Lin, K.-H. Chuang, W.-J. Lin, S. Yeh, L. A. Hanchett, M. M. Rahman, H.-Y. Kang, M.-Y. Tsai, Y. Zhang, et al.
Interruption of Nuclear Factor {kappa}B Signaling by the Androgen Receptor Facilitates 12-O-Tetradecanoylphorbolacetate-Induced Apoptosis in Androgen-sensitive Prostate Cancer LNCaP Cells
Cancer Res., November 1, 2003; 63(21): 7106 - 7112.
[Abstract] [Full Text] [PDF]

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 Mol. Pharmacol.Home page
S. W. Chung, B. Y. Kang, and T. S. Kim
Inhibition of Interleukin-4 Production in CD4+ T Cells by Peroxisome Proliferator-Activated Receptor-{gamma} (PPAR-{gamma}) Ligands: Involvement of Physical Association between PPAR-{gamma} and the Nuclear Factor of Activated T Cells Transcription Factor
Mol. Pharmacol., November 1, 2003; 64(5): 1169 - 1179.
[Abstract] [Full Text] [PDF]

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 FASEB J.Home page
T. RHEN, S. GRISSOM, C. AFSHARI, and J. A. CIDLOWSKI
Dexamethasone blocks the rapid biological effects of 17{beta}-estradiol in the rat uterus without antagonizing its global genomic actions
FASEB J, October 1, 2003; 17(13): 1849 - 1870.
[Abstract] [Full Text] [PDF]

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 J. Lipid Res.Home page
L. Sun, A. C. Nicholson, D. P. Hajjar, A. M. Gotto Jr., and J. Han
Adipogenic differentiating agents regulate expression of fatty acid binding protein and CD36 in the J744 macrophage cell line
J. Lipid Res., October 1, 2003; 44(10): 1877 - 1886.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
J. Frasor, J. M. Danes, B. Komm, K. C. N. Chang, C. R. Lyttle, and B. S. Katzenellenbogen
Profiling of Estrogen Up- and Down-Regulated Gene Expression in Human Breast Cancer Cells: Insights into Gene Networks and Pathways Underlying Estrogenic Control of Proliferation and Cell Phenotype
Endocrinology, October 1, 2003; 144(10): 4562 - 4574.
[Abstract] [Full Text] [PDF]

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 Am. J. PsychiatryHome page
C. L. Raison and A. H. Miller
When Not Enough Is Too Much: The Role of Insufficient Glucocorticoid Signaling in the Pathophysiology of Stress-Related Disorders
Am J Psychiatry, September 1, 2003; 160(9): 1554 - 1565.
[Abstract] [Full Text] [PDF]

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 Endocr. Rev.Home page
K. De Bosscher, W. Vanden Berghe, and G. Haegeman
The Interplay between the Glucocorticoid Receptor and Nuclear Factor-{kappa}B or Activator Protein-1: Molecular Mechanisms for Gene Repression
Endocr. Rev., August 1, 2003; 24(4): 488 - 522.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
G.U. Meduri, P. Carratu, and A.X. Freire
Evidence of biological efficacy for prolonged glucocorticoid treatment in patients with unresolving ARDS
Eur. Respir. J., August 1, 2003; 22(42_suppl): 57s - 64s.
[Abstract] [Full Text] [PDF]

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 JCBHome page
D. Soulet and S. Rivest
Polyamines play a critical role in the control of the innate immune response in the mouse central nervous system
J. Cell Biol., July 21, 2003; 162(2): 257 - 268.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
K. Wang, D. Scheel-Toellner, S. H. Wong, R. Craddock, J. Caamano, A. N. Akbar, M. Salmon, and J. M. Lord
Inhibition of Neutrophil Apoptosis by Type 1 IFN Depends on Cross-Talk Between Phosphoinositol 3-Kinase, Protein Kinase C-{delta}, and NF-{kappa}B Signaling Pathways
J. Immunol., July 15, 2003; 171(2): 1035 - 1041.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
S. Nadeau and S. Rivest
Glucocorticoids Play a Fundamental Role in Protecting the Brain during Innate Immune Response
J. Neurosci., July 2, 2003; 23(13): 5536 - 5544.
[Abstract] [Full Text] [PDF]

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 Arch SurgHome page
J. F. Kuebler, Y. Yokoyama, D. Jarrar, B. Toth, L. W. Rue III, K. I. Bland, P. Wang, and I. H. Chaudry
Administration of Progesterone After Trauma and Hemorrhagic Shock Prevents Hepatocellular Injury
Arch Surg, July 1, 2003; 138(7): 727 - 734.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
F. A. Patel, J. W. Funder, and J. R. G. Challis
Mechanism of Cortisol/Progesterone Antagonism in the Regulation of 15-Hydroxyprostaglandin Dehydrogenase Activity and Messenger Ribonucleic Acid Levels in Human Chorion and Placental Trophoblast Cells at Term
J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2922 - 2933.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
A. Mouihate and Q. J. Pittman
Neuroimmune Response to Endogenous and Exogenous Pyrogens Is Differently Modulated by Sex Steroids
Endocrinology, June 1, 2003; 144(6): 2454 - 2460.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
R. Marienfeld, M. J. May, I. Berberich, E. Serfling, S. Ghosh, and M. Neumann
RelB Forms Transcriptionally Inactive Complexes with RelA/p65
J. Biol. Chem., May 23, 2003; 278(22): 19852 - 19860.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
A. J. Casal, J.-S. Silvestre, C. Delcayre, and A. M. Capponi
Expression and Modulation of Steroidogenic Acute Regulatory Protein Messenger Ribonucleic Acid in Rat Cardiocytes and after Myocardial Infarction
Endocrinology, May 1, 2003; 144(5): 1861 - 1868.
[Abstract] [Full Text] [PDF]

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 Reproductive SciencesHome page
S. Gupta, S. Gyomorey, S. J. Lye, W. Gibb, and J. R. G. Challis
Effect of Labor on Glucocorticoid Receptor (GRTotal, GR{alpha}, and GR{beta}) Proteins in Ovine Intrauterine Tissues
Reproductive Sciences, April 1, 2003; 10(3): 136 - 144.
[Abstract] [PDF]

Home page
 Mol. Endocrinol.Home page
C. Lukas-Croisier, C. Lasala, J. Nicaud, P. Bedecarras, T. R. Kumar, M. Dutertre, M. M. Matzuk, J.-Y. Picard, N. Josso, and R. Rey
Follicle-Stimulating Hormone Increases Testicular Anti-Mullerian Hormone (AMH) Production through Sertoli Cell Proliferation and a Nonclassical Cyclic Adenosine 5'-Monophosphate-Mediated Activation of the AMH Gene
Mol. Endocrinol., April 1, 2003; 17(4): 550 - 561.
[Abstract] [Full Text] [PDF]


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