help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gabay, C.
Right arrow Articles by Meier, C. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gabay, C.
Right arrow Articles by Meier, C. A.
The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 2 783-791
Copyright © 2001 by The Endocrine Society

Original Studies

Leptin Directly Induces the Secretion of Interleukin 1 Receptor Antagonist in Human Monocytes1

Cem Gabay2, Magali G. Dreyer2, Nathalie Pellegrinelli, Rachel Chicheportiche and Christoph A. Meier

Department of Internal Medicine, Division of Rheumatology (C.G., N.P.), Division of Endocrinology and Diabetes (M.G.D., C.A.M.), and Division of Immunology and Allergy (R.C.), University Hospital Geneva, CH-1211 Geneva, Switzerland

Address correspondence and requests for reprints to: Dr. Christoph A. Meier, Division of Endocrinology and Diabetes, University Hospital Geneva, 24, rue Micheli-du-Crest, 1211 Geneva 14, Switzerland. E-mail: cameier{at}bluewin.ch

Besides its actions on the regulation of appetite, leptin has also been implicated in regulating reproductive and immune functions. Because leptin-deficient mice are more susceptible to lipopolysaccharide- and tumor necrosis factor-{alpha}-induced shock, which is associated with lower levels of interleukin 1 receptor antagonist (IL-1Ra), we investigated whether leptin is a direct regulator of IL-1Ra in human monocytes. In human moncytic cells, leptin was capable of inducing a 6- to 10-fold increase in secreted IL-1Ra in a time- and dose-dependent manner. Moreover, leptin induced the messenger RNA for IL-1Ra within 8 h and specifically activated the promoter for this gene. However, leptin had no effect on the expression or secretion of IL-1 in THP-1 cells. This effect of leptin on monocytic cells requires the presence of the functional leptin receptor OB-Rb, which we have shown to be present in human monocytes by RT-PCR and by measuring the activation of the Jak/STAT pathway.

In summary, we have demonstrated that leptin is capable of inducing the expression and secretion of IL-1Ra by human monocytes, an effect that is potentially mediated through the presence of functional leptin receptors on these cells. These findings suggest that leptin may have immunomodulatory functions in vivo.




This article has been cited by other articles:


Home page
 JEMHome page
D. Gaucher, R. Therrien, N. Kettaf, B. R. Angermann, G. Boucher, A. Filali-Mouhim, J. M. Moser, R. S. Mehta, D. R. Drake III, E. Castro, et al.
Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses
J. Exp. Med., December 22, 2008; 205(13): 3119 - 3131.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
S. Thalmann and C. A. Meier
Local adipose tissue depots as cardiovascular risk factors
Cardiovasc Res, September 1, 2007; 75(4): 690 - 701.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
E. A. Oral, E. D. Javor, L. Ding, G. Uzel, E. K. Cochran, J. R. Young, A. M. DePaoli, S. M. Holland, and P. Gorden
Leptin Replacement Therapy Modulates Circulating Lymphocyte Subsets and Cytokine Responsiveness in Severe Lipodystrophy
J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 621 - 628.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Martin, R. de Vittoris, V. David, R. Moraes, M. Begeot, M.-H. Lafage-Proust, C. Alexandre, L. Vico, and T. Thomas
Leptin Modulates both Resorption and Formation while Preventing Disuse-Induced Bone Loss in Tail-Suspended Female Rats
Endocrinology, August 1, 2005; 146(8): 3652 - 3659.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Molnarfi, N. Hyka-Nouspikel, L. Gruaz, J.-M. Dayer, and D. Burger
The Production of IL-1 Receptor Antagonist in IFN-{beta}-Stimulated Human Monocytes Depends on the Activation of Phosphatidylinositol 3-Kinase but Not of STAT1
J. Immunol., March 1, 2005; 174(5): 2974 - 2980.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
J. W. Bullen Jr, M. Ziotopoulou, L. Ungsunan, J. Misra, I. Alevizos, E. Kokkotou, E. Maratos-Flier, G. Stephanopoulos, and C. S. Mantzoros
Short-term resistance to diet-induced obesity in A/J mice is not associated with regulation of hypothalamic neuropeptides
Am J Physiol Endocrinol Metab, October 1, 2004; 287(4): E662 - E670.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
L. Ottonello, P. Gnerre, M. Bertolotto, M. Mancini, P. Dapino, R. Russo, G. Garibotto, T. Barreca, and F. Dallegri
Leptin as a Uremic Toxin Interferes with Neutrophil Chemotaxis
J. Am. Soc. Nephrol., September 1, 2004; 15(9): 2366 - 2372.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
C. E. Juge-Aubry, E. Somm, R. Chicheportiche, D. Burger, A. Pernin, B. Cuenod-Pittet, P. Quinodoz, V. Giusti, J.-M. Dayer, and C. A. Meier
Regulatory Effects of Interleukin (IL)-1, Interferon-{beta}, and IL-4 on the Production of IL-1 Receptor Antagonist by Human Adipose Tissue
J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2652 - 2658.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
K. Maedler, P. Sergeev, J. A. Ehses, Z. Mathe, D. Bosco, T. Berney, J.-M. Dayer, M. Reinecke, P. A. Halban, and M. Y. Donath
Leptin modulates {beta} cell expression of IL-1 receptor antagonist and release of IL-1{beta} in human islets
PNAS, May 25, 2004; 101(21): 8138 - 8143.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
S. Gaige, E. Abou, A. Abysique, and M. Bouvier
Effects of interactions between interleukin-1{beta} and leptin on cat intestinal vagal mechanoreceptors
J. Physiol., February 15, 2004; 555(1): 297 - 310.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. Zarkesh-Esfahani, A. G. Pockley, Z. Wu, P. G. Hellewell, A. P. Weetman, and R. J. M. Ross
Leptin Indirectly Activates Human Neutrophils via Induction of TNF-{alpha}
J. Immunol., February 1, 2004; 172(3): 1809 - 1814.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
N. K. Ryan, K. H. Van der Hoek, S. A. Robertson, and R. J. Norman
Leptin and Leptin Receptor Expression in the Rat Ovary
Endocrinology, November 1, 2003; 144(11): 5006 - 5013.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
E. Xiao, L. Xia-Zhang, N. R. Vulliemoz, M. Ferin, and S. L. Wardlaw
Leptin Modulates Inflammatory Cytokine and Neuroendocrine Responses to Endotoxin in the Primate
Endocrinology, October 1, 2003; 144(10): 4350 - 4353.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
G Palmer and C Gabay
A role for leptin in rheumatic diseases?
Ann Rheum Dis, October 1, 2003; 62(10): 913 - 915.
[Full Text]

Home page
 Ann Rheum DisHome page
M Bokarewa, D Bokarew, O Hultgren, and A Tarkowski
Leptin consumption in the inflamed joints of patients with rheumatoid arthritis
Ann Rheum Dis, October 1, 2003; 62(10): 952 - 956.
[Abstract] [Full Text]

Home page
 DiabetesHome page
C. E. Juge-Aubry, E. Somm, V. Giusti, A. Pernin, R. Chicheportiche, C. Verdumo, F. Rohner-Jeanrenaud, D. Burger, J.-M. Dayer, and C. A. Meier
Adipose Tissue Is a Major Source of Interleukin-1 Receptor Antagonist: Upregulation in Obesity and Inflammation
Diabetes, May 1, 2003; 52(5): 1104 - 1110.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
T. Ueland, C. Kristo, K. Godang, P. Aukrust, and J. Bollerslev
Interleukin-1 Receptor Antagonist Is Associated with Fat Distribution in Endogenous Cushing's Syndrome: A Longitudinal Study
J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1492 - 1496.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
R. R. Gonzalez, K. Leary, J. C. Petrozza, and P. C. Leavis
Leptin regulation of the interleukin-1 system in human endometrial cells
Mol. Hum. Reprod., March 1, 2003; 9(3): 151 - 158.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
C. A. Meier, E. Bobbioni, C. Gabay, F. Assimacopoulos-Jeannet, A. Golay, and J.-M. Dayer
IL-1 Receptor Antagonist Serum Levels Are Increased in Human Obesity: A Possible Link to the Resistance to Leptin?
J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1184 - 1188.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Busso, A. So, V. Chobaz-Peclat, C. Morard, E. Martinez-Soria, D. Talabot-Ayer, and C. Gabay
Leptin Signaling Deficiency Impairs Humoral and Cellular Immune Responses and Attenuates Experimental Arthritis
J. Immunol., January 15, 2002; 168(2): 875 - 882.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
R. FAGGIONI, K. R. FEINGOLD, and C. GRUNFELD
Leptin regulation of the immune response and the immunodeficiency of malnutrition
FASEB J, December 1, 2001; 15(14): 2565 - 2571.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2001 by The Endocrine Society