![]()
|
|
||||||||
Our previous studies in human monocytes have demonstrated that
interleukin (IL)-10 inhibits lipopolysaccharide (LPS)-stimulated
production of inflammatory cytokines, IL-1
Volume 270,
Number 16,
Issue of April 21, pp. 9558-9563, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
B (NF
B) Activation in Human
Monocytes
IL-10 AND IL-4 SUPPRESS CYTOKINE SYNTHESIS BY DIFFERENT MECHANISMS
, IL-6, IL-8, and tumor
necrosis factor (TNF)-
by blocking gene transcription. Using
electrophoretic mobility shift assays (EMSA), we now show that, in
monocytes stimulated with LPS or TNF
, IL-10 inhibits nuclear
localization of nuclear factor
B (NF
B), a transcription
factor involved in the expression of inflammatory cytokine genes.
Several other transcription factors including NF-IL-6, AP-1, AP-2, GR,
CREB, Oct-1, and Sp-1 are not affected by IL-10. This selective
inhibition by IL-10 of NF
B activation occurs rapidly and in a
dose-dependent manner and correlates well with IL-10's cytokine
synthesis inhibitory activity in terms of both kinetics and dose
responsiveness. Furthermore, compounds such as tosylphenylalanyl
chloromethyl ketone and pyrrolidinedithiocarbamate that are known to
selectively inhibit NF
B activation block cytokine gene
transcription in LPS-stimulated monocytes. Taken together, these
results suggest that inhibition of NF
B activation may be an
important mechanism for IL-10 supression of cytokine gene transcription
in human monocytes. IL-4, another cytokine that inhibits cytokine mRNA
accumulation in monocytes, shows little inhibitory effect on
LPS-induced NF
B activation. Further examination reveals that,
unlike IL-10, IL-4 enhances mRNA degradation and does not suppress
cytokine gene transcription. These data indicate that IL-10 and IL-4
inhibit cytokine production by different mechanisms.
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
![]() |
J. Flores, H. L. DuPont, S. A. Lee, J. Belkind-Gerson, M. Paredes, J. A. Mohamed, L. Y. Armitige, D.-C. Guo, and P. C. Okhuysen Influence of Host Interleukin-10 Polymorphisms on Development of Traveler's Diarrhea Due to Heat-Labile Enterotoxin-Producing Escherichia coli in Travelers from the United States Who Are Visiting Mexico Clin. Vaccine Immunol., August 1, 2008; 15(8): 1194 - 1198. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Muhlbauer, P. M. Chilton, T. C. Mitchell, and C. Jobin Impaired Bcl3 Up-regulation Leads to Enhanced Lipopolysaccharide-induced Interleukin (IL)-23P19 Gene Expression in IL-10-/- Mice J. Biol. Chem., May 23, 2008; 283(21): 14182 - 14189. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Dagvadorj, Y. Naiki, G. Tumurkhuu, F. Hassan, S. Islam, N. Koide, I. Mori, T. Yoshida, and T. Yokochi Interleukin-10 inhibits tumor necrosis factor-{alpha} production in lipopolysaccharide-stimulated RAW 264.7 cells through reduced MyD88 expression Innate Immunity, April 1, 2008; 14(2): 109 - 115. [Abstract] [PDF] |
||||
![]() |
R. P Miech Pathopharmacology of Excessive Hemorrhage in Mifepristone Abortions Ann. Pharmacother., December 1, 2007; 41(12): 2002 - 2007. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Lim, J.-P. Collet, S. Moutereau, N. Guigui, L. Mitchell-Heggs, S. Loric, M. Bernard, S. Benhamed, G. Montalescot, J.-L. D. Rande, et al. Fetuin-A Is an Independent Predictor of Death after ST-Elevation Myocardial Infarction Clin. Chem., October 1, 2007; 53(10): 1835 - 1840. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. K. Weaver, E. Bohn, B. A. Judd, M. P. Gil, and R. D. Schreiber ABIN-3: a Molecular Basis for Species Divergence in Interleukin-10-Induced Anti-Inflammatory Actions Mol. Cell. Biol., July 1, 2007; 27(13): 4603 - 4616. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. M. Williams, U. Sarma, K. Willets, T. Smallie, F. Brennan, and B. M. J. Foxwell Expression of Constitutively Active STAT3 Can Replicate the Cytokine-suppressive Activity of Interleukin-10 in Human Primary Macrophages J. Biol. Chem., March 9, 2007; 282(10): 6965 - 6975. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. A. Fraser, M. Arora, S. S. Bohlson, E. Lozano, and A. J. Tenner Generation of Inhibitory NF{kappa}B Complexes and Phosphorylated cAMP Response Element-binding Protein Correlates with the Anti-inflammatory Activity of Complement Protein C1q in Human Monocytes J. Biol. Chem., March 9, 2007; 282(10): 7360 - 7367. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. N. Tziakas, G. K. Chalikias, C. O. Antonoglou, S. Veletza, I. K. Tentes, A. X. Kortsaris, D. I. Hatseras, and J. C. Kaski Apolipoprotein E Genotype and Circulating Interleukin-10 Levels in Patients With Stable and Unstable Coronary Artery Disease J. Am. Coll. Cardiol., December 19, 2006; 48(12): 2471 - 2481. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Shahrara, C. C. Park, V. Temkin, J. W. Jarvis, M. V. Volin, and R. M. Pope RANTES Modulates TLR4-Induced Cytokine Secretion in Human Peripheral Blood Monocytes J. Immunol., October 15, 2006; 177(8): 5077 - 5087. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Folch-Puy, S. Granell, J. C. Dagorn, J. L. Iovanna, and D. Closa Pancreatitis-Associated Protein I Suppresses NF-{kappa}B Activation through a JAK/STAT-Mediated Mechanism in Epithelial Cells J. Immunol., March 15, 2006; 176(6): 3774 - 3779. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Qasimi, A. Ming-Lum, A. Ghanipour, C. J. Ong, M. E. Cox, J. Ihle, N. Cacalano, A. Yoshimura, and A. L-F. Mui Divergent Mechanisms Utilized by SOCS3 to Mediate Interleukin-10 Inhibition of Tumor Necrosis Factor {alpha} and Nitric Oxide Production by Macrophages J. Biol. Chem., March 10, 2006; 281(10): 6316 - 6324. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Gafa, R. Lande, M. C. Gagliardi, M. Severa, E. Giacomini, M. E. Remoli, R. Nisini, C. Ramoni, P. Di Francesco, D. Aldebert, et al. Human Dendritic Cells following Aspergillus fumigatus Infection Express the CCR7 Receptor and a Differential Pattern of Interleukin-12 (IL-12), IL-23, and IL-27 Cytokines, Which Lead to a Th1 Response Infect. Immun., March 1, 2006; 74(3): 1480 - 1489. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Mu, X. Ouyang, A. Agarwal, L. Zhang, D. A. Long, P. E. Cruz, C. A. Roncal, O. Y. Glushakova, V. A. Chiodo, M. A. Atkinson, et al. IL-10 Suppresses Chemokines, Inflammation, and Fibrosis in a Model of Chronic Renal Disease J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3651 - 3660. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Fan, N. M. Heller, M. Gorospe, U. Atasoy, and C. Stellato The role of post-transcriptional regulation in chemokine gene expression in inflammation and allergy Eur. Respir. J., November 1, 2005; 26(5): 933 - 947. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. W. DePaolo, R. Lathan, B. J. Rollins, and W. J. Karpus The Chemokine CCL2 Is Required for Control of Murine Gastric Salmonella enterica Infection Infect. Immun., October 1, 2005; 73(10): 6514 - 6522. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-J. Li and C.-H. Fang Effects of 4 Weeks of Atorvastatin Administration on the Antiinflammatory Cytokine Interleukin-10 in Patients with Unstable Angina Clin. Chem., September 1, 2005; 51(9): 1735 - 1738. [Full Text] [PDF] |
||||
![]() |
P. J. Murray The primary mechanism of the IL-10-regulated antiinflammatory response is to selectively inhibit transcription PNAS, June 14, 2005; 102(24): 8686 - 8691. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. K. Andersson, M. Chaduvula, S. E. Atkinson, S. Khanolkar-Young, S. Jain, L. Suneetha, S. Suneetha, and D. N. J. Lockwood Effects of Prednisolone Treatment on Cytokine Expression in Patients with Leprosy Type 1 Reactions Infect. Immun., June 1, 2005; 73(6): 3725 - 3733. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Furukawa, K. Oshima, T. Tung, G. Cui, H. Laks, and L. Sen Liposome-Mediated Combinatorial Cytokine Gene Therapy Induces Localized Synergistic Immunosuppression and Promotes Long-Term Survival of Cardiac Allografts J. Immunol., June 1, 2005; 174(11): 6983 - 6992. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Hoentjen, R. B. Sartor, M. Ozaki, and C. Jobin STAT3 regulates NF-{kappa}B recruitment to the IL-12p40 promoter in dendritic cells Blood, January 15, 2005; 105(2): 689 - 696. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Grutz New insights into the molecular mechanism of interleukin-10-mediated immunosuppression J. Leukoc. Biol., January 1, 2005; 77(1): 3 - 15. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Srisodsai, R. Kurotani, Y. Chiba, F. Sheikh, H. A. Young, R. P. Donnelly, and S. Kimura Interleukin-10 Induces Uteroglobin-related Protein (UGRP) 1 Gene Expression in Lung Epithelial Cells through Homeodomain Transcription Factor T/EBP/NKX2.1 J. Biol. Chem., December 24, 2004; 279(52): 54358 - 54368. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. M. Thackray, A. N. McKenzie, M. A. Klein, A. Lauder, and R. Bujdoso Accelerated Prion Disease in the Absence of Interleukin-10 J. Virol., December 15, 2004; 78(24): 13697 - 13707. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Specht, L. Volkmann, T. Wynn, and A. Hoerauf Interleukin-10 (IL-10) Counterregulates IL-4-Dependent Effector Mechanisms in Murine Filariasis Infect. Immun., November 1, 2004; 72(11): 6287 - 6293. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Aggarwal, Y. Takada, A. M. Mhashilkar, K. Sieger, S. Chada, and B. B. Aggarwal Melanoma Differentiation-Associated Gene-7/IL-24 Gene Enhances NF-{kappa}B Activation and Suppresses Apoptosis Induced by TNF J. Immunol., October 1, 2004; 173(7): 4368 - 4376. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. A. Ricchetti, L. M. Williams, and B. M. J. Foxwell Heme oxygenase 1 expression induced by IL-10 requires STAT-3 and phosphoinositol-3 kinase and is inhibited by lipopolysaccharide J. Leukoc. Biol., September 1, 2004; 76(3): 719 - 726. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. J. Moos, K. Edes, J. E. Mullally, and F. A. Fitzpatrick Curcumin impairs tumor suppressor p53 function in colon cancer cells Carcinogenesis, September 1, 2004; 25(9): 1611 - 1617. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Bhattacharyya, P. Sen, M. Wallet, B. Long, A. S. Baldwin Jr, and R. Tisch Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K/Akt pathway and of I{kappa}B kinase activity Blood, August 15, 2004; 104(4): 1100 - 1109. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Potteaux, B. Esposito, O. van Oostrom, V. Brun, P. Ardouin, H. Groux, A. Tedgui, and Z. Mallat Leukocyte-Derived Interleukin 10 Is Required for Protection Against Atherosclerosis in Low-Density Lipoprotein Receptor Knockout Mice Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1474 - 1478. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Mazighi, A. Pelle, W. Gonzalez, E. M. Mtairag, M. Philippe, D. Henin, J.-B. Michel, and L. J. Feldman IL-10 inhibits vascular smooth muscle cell activation in vitro and in vivo Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H866 - H871. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Galgani, V. De Rosa, S. De Simone, A. Leonardi, U. D'Oro, G. Napolitani, A. M. Masci, S. Zappacosta, and L. Racioppi Cyclic AMP Modulates the Functional Plasticity of Immature Dendritic Cells by Inhibiting Src-like Kinases through Protein Kinase A-mediated Signaling J. Biol. Chem., July 30, 2004; 279(31): 32507 - 32514. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Schieffer, C. Bunte, J. Witte, K. Hoeper, R. H. Boger, E. Schwedhelm, and H. Drexler Comparative effects of AT1-antagonism and angiotensin-converting enzyme inhibition on markers of inflammation and platelet aggregation in patients with coronary artery disease J. Am. Coll. Cardiol., July 21, 2004; 44(2): 362 - 368. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. A. Clark, L. M. Alleva, A. C. Mills, and W. B. Cowden Pathogenesis of Malaria and Clinically Similar Conditions Clin. Microbiol. Rev., July 1, 2004; 17(3): 509 - 539. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. L. Chelvarajan, S. M. Collins, I. E. Doubinskaia, S. Goes, J. Van Willigen, D. Flanagan, W. J. S. de Villiers, J. S. Bryson, and S. Bondada Defective macrophage function in neonates and its impact on unresponsiveness of neonates to polysaccharide antigens J. Leukoc. Biol., June 1, 2004; 75(6): 982 - 994. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Le Tulzo, C. Pangault, L. Amiot, V. Guilloux, O. Tribut, C. Arvieux, C. Camus, R. Fauchet, R. Thomas, and B. Drenou Monocyte Human Leukocyte Antigen-DR Transcriptional Downregulation by Cortisol during Septic Shock Am. J. Respir. Crit. Care Med., May 15, 2004; 169(10): 1144 - 1151. [Abstract] [Full Text] [PDF] |
||||
![]() |
H.-J. Kim, J. Hart, N. Knatz, M. W. Hall, and M. D. Wewers Janus Kinase 3 Down-Regulates Lipopolysaccharide-Induced IL-1{beta}-Converting Enzyme Activation by Autocrine IL-10 J. Immunol., April 15, 2004; 172(8): 4948 - 4955. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. O. Scumpia, P. J. Sarcia, K. M. Kelly, V. G. DeMarco, and J. W. Skimming Hypothermia Induces Anti-Inflammatory Cytokines and Inhibits Nitric Oxide and Myeloperoxidase-Mediated Damage in the Hearts of Endotoxemic Rats Chest, April 1, 2004; 125(4): 1483 - 1491. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Zhou, A. A. Nazarian, and S. T. Smale Interleukin-10 Inhibits Interleukin-12 p40 Gene Transcription by Targeting a Late Event in the Activation Pathway Mol. Cell. Biol., March 15, 2004; 24(6): 2385 - 2396. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Inoue, T. Otsuka, H. Niiro, S. Nagano, Y. Arinobu, E. Ogami, M. Akahoshi, K. Miyake, I. Ninomiya, S. Shimizu, et al. Novel Regulatory Mechanisms of CD40-Induced Prostanoid Synthesis by IL-4 and IL-10 in Human Monocytes J. Immunol., February 15, 2004; 172(4): 2147 - 2154. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. R. Karpf, A. W. Lasek, T. O. Ririe, A. N. Hanks, D. Grossman, and D. A. Jones Limited Gene Activation in Tumor and Normal Epithelial Cells Treated with the DNA Methyltransferase Inhibitor 5-Aza-2'-deoxycytidine Mol. Pharmacol., January 1, 2004; 65(1): 18 - 27. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Williams, L. Bradley, A. Smith, and B. Foxwell Signal Transducer and Activator of Transcription 3 Is the Dominant Mediator of the Anti-Inflammatory Effects of IL-10 in Human Macrophages J. Immunol., January 1, 2004; 172(1): 567 - 576. [Abstract] [Full Text] [PDF] |
||||
![]() |
A.-S. W. Moller, R. Ovstebo, A.-B. Westvik, G. B. Joo, K.-B. F. Haug, and P. Kierulf Effects of bacterial cell wall components (PAMPs) on the expression of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1{alpha} (MIP-1{alpha}) and the chemokine receptor CCR2 by purified human blood monocytes Innate Immunity, December 1, 2003; 9(6): 349 - 360. [Abstract] [PDF] |
||||
![]() |
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] |
||||
![]() |
R. R. Brubaker Interleukin-10 and Inhibition of Innate Immunity to Yersiniae: Roles of Yops and LcrV (V Antigen) Infect. Immun., July 1, 2003; 71(7): 3673 - 3681. [Full Text] [PDF] |
||||
![]() |
M. Jin, H. J. Jung, J. J. Choi, H. Jeon, J. H. Oh, B. Kim, S. S. Shin, J. K. Lee, K. Yoon, and S. Kim Activation of Selective Transcription Factors and Cytokines by Water-Soluble Extract from Lentinus lepideus Experimental Biology and Medicine, June 1, 2003; 228(6): 749 - 758. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Asadullah, W. Sterry, and H. D. Volk Interleukin-10 Therapy--Review of a New Approach Pharmacol. Rev., June 1, 2003; 55(2): 241 - 269. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Heeschen, S. Dimmeler, C. W. Hamm, S. Fichtlscherer, E. Boersma, M. L. Simoons, A. M. Zeiher, and for the CAPTURE Study Investigators Serum Level of the Antiinflammatory Cytokine Interleukin-10 Is an Important Prognostic Determinant in Patients With Acute Coronary Syndromes Circulation, April 29, 2003; 107(16): 2109 - 2114. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. C.-J. Cheeran, S. Hu, W. S. Sheng, P. K. Peterson, and J. R. Lokensgard CXCL10 Production from Cytomegalovirus-Stimulated Microglia Is Regulated by both Human and Viral Interleukin-10 J. Virol., April 15, 2003; 77(8): 4502 - 4515. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Macdonald, H. F. Galley, and N. R. Webster Oxidative stress and gene expression in sepsis Br. J. Anaesth., February 1, 2003; 90(2): 221 - 232. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. A. Sato, J. A. Keelan, and M. D. Mitchell Critical Paracrine Interactions Between TNF-{alpha} and IL-10 Regulate Lipopolysaccharide-Stimulated Human Choriodecidual Cytokine and Prostaglandin E2 Production J. Immunol., January 1, 2003; 170(1): 158 - 166. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Ikeda, K. Sato, N. Kuwada, T. Matsumura, T. Yamashita, F. Kimura, K. Hatake, K. Ikeda, and K. Motoyoshi Interleukin-10 differently regulates monocyte chemoattractant protein-1 gene expression depending on the environment in a human monoblastic cell line, UG3 J. Leukoc. Biol., December 1, 2002; 72(6): 1198 - 1205. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Mahalingam and B. A. Lidbury Suppression of lipopolysaccharide-induced antiviral transcription factor (STAT-1 and NF-kappa B) complexes by antibody-dependent enhancement of macrophage infection by Ross River virus PNAS, October 15, 2002; 99(21): 13819 - 13824. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Caamano and C. A. Hunter NF-{kappa}B Family of Transcription Factors: Central Regulators of Innate and Adaptive Immune Functions Clin. Microbiol. Rev., July 1, 2002; 15(3): 414 - 429. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Berlato, M. A. Cassatella, I. Kinjyo, L. Gatto, A. Yoshimura, and F. Bazzoni Involvement of Suppressor of Cytokine Signaling-3 as a Mediator of the Inhibitory Effects of IL-10 on Lipopolysaccharide-Induced Macrophage Activation J. Immunol., June 15, 2002; 168(12): 6404 - 6411. [Abstract] [Full Text] [PDF] |
||||
![]() |
|