Effect of Leptin on the Expression of Lipopolysaccharide-Induced Chemokine KC mRNA in the Mouse Peritoneal Macrophages

  • Lee, Dong-Eun (Department of Plastic Surgery, College of Medicine, Yeungnam University) ;
  • Kim, Hyo-Young (Department of Microbiology, College of Medicine, yeungnam University) ;
  • Song, In-Hwan (Department of Anatomy, College of Medicine, Yeungnam University) ;
  • Kim, Sung-Kwang (Department of Microbiology, College of Medicine, Yeungnam University) ;
  • Seul, Jung-Hyun (Department of Plastic Surgery, College of Medicine, Yeungnam University) ;
  • Kim, Hee-Sun (Department of Microbiology, College of Medicine, Yeungnam University)
  • Published : 2004.08.01

Abstract

Leptin is an adipocyte-secreted hormone and its plasma levels correlate with total body fat mass, however, it also plays a regulatory role in immunity, inflammation, and hematopoiesis. Chemokine is known as a chemoattractant cytokine in inflammatory reaction, but its role in leptin reaction has not been well studied. In this study, the direct effect of leptin on the expression of chemokine mRNAs and lipopolysaccharide (LPS)-induced chemokine KC mRNA in mouse peritoneal macrophages was investigated. Leptin did not induce the expression of lymphotactin, RANTES, eotaxin, MIP-1$\beta$, MIP-1$\alpha$, MIP-2, MCP-1, IP-10, TCA-3, and KC mRNA in mouse peritoneal macrophages, and had no direct effect on the expression of these LPS-induced chemokine mRNAs except KC mRNA. The synergistic effect of leptin on the expression of LPS-induced KC mRNA occurred late in the time course of response to LPS. The increased expressions of Ob-Rb mRNA and leptin receptor protein were detected during the LPS treatment. Leptin produced a substantial increase in the stability of the LPS-induced KC mRNA, and the synergistic effect of leptin on LPS-induced KC mRNA expression was further augmented by cycloheximide (CHX). Pyrrolidine dithiocarbamate (PDTC) did not block the synergistic effect of leptin on LPS-induced KC mRNA expression in mouse peritoneal macrophages. These data suggest that although leptin has no direct effect on the expression of lymphotactin, RANTES, eotaxin, MIP-1$\beta$, MIP-1$\alpha$, MIP-2, MCP-1, IP-10, TCA-3, and KC mRNA in mouse peritoneal macrophages, the synergistic effect of leptin on the expression of LPS-induced KC mRNA has the possibility that LPS might induce the expression of the Ob-Rb receptor or an unknown gene(s) that sensitizes macrophages to the synergistic function of leptin. Therefore, further studies are necessary to examine leptin as a regulatory factor of chemokine production.

Keywords

References

  1. Am. J. Physiol. Gastrointest. Liver Physiol. v.281 Effect of CXC chemokines on neutrophil activation and sequestration in hepatic vasculature Bajt, M. Y.;A. Farhood;H. Jaeschke https://doi.org/10.1152/ajpgi.2001.281.5.G1188
  2. FASEB J. v.13 Leptin induces oxidative stress in human endothelial cells Bouloumie, A.;T. Marumo;M. Lafontan;R. Busse https://doi.org/10.1096/fasebj.13.10.1231
  3. J. Immunol. v.154 Expression and biologic characterization of the murine chemokine KC Bozic, C. R.;L. F. Kolakowski;N. P. Gerard;C. Garcia-Rodriguez;U. G. Claudia;M. J. Conklyn;R. Breslow;H. J. Showell;C. Gerard
  4. Am. J. Physiol. v.276 Leptin deficiency enhances sensitivity to endotoxin-induced lethality Faggioni, R.;G. Fantuzzi;C. Gabay;A. Moser;C. A. Dinarello;K. R. Peingold;C. Grunfeld https://doi.org/10.1152/ajpcell.1999.276.1.C136
  5. J. Leukoc. Biol. v.68 Leptin in the regulation of immunity, inflammation, and hematopoiesis Fantuzzi, G.;R. Faggioni
  6. Proc. Natl. Acad. Sci. USA v.94 Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues Fei, H.;H. J. Okano;C. Li;G. H. Lee;C. Zaho;R. Darnell;J. M. Friedman https://doi.org/10.1073/pnas.94.13.7001
  7. Proc. Natl. Acad. Sci. USA v.93 Defective STAT signaling by the leptin receptor in diabetic mice Ghilardi, C.;S. Ziegler;A. Wiestner;R. Stoffel;M. H. Heim;R. C. Skoda https://doi.org/10.1073/pnas.93.13.6231
  8. J. Immunol. v.167 High-dose leptin activates human leukocytes via receptor expression on monocytes Hamid, Z. E.;G. Pockley;R. A. Metcalfe;M. Bidlingmaier;Z. Wu;A. Ajami;A. P. Weetman;C. J. Strasburger https://doi.org/10.4049/jimmunol.167.8.4593
  9. Domest. Anim. Endocrinol. v.15 Leptin and its receptors: Regulators of whole-body energy homeostasis Houseknecht, K. L.;C. P. Portcarrero https://doi.org/10.1016/S0739-7240(98)00035-6
  10. J. Microbiol. Biotechnol. v.13 Purification of chitinase from an antagonistic bacterium Bacillus sp. 7079 and pro-inflammatory cytokine gene expression by PCTC Han, O. K.;E. T. Lee;Y. S. Lee;S.-D. Kim
  11. Cell. Immunol. v.194 Human leptin stimulates proliferation and activation of human circulating monocytes Jose, S. A.;G. Raimundo;S. M. Victor https://doi.org/10.1006/cimm.1999.1490
  12. J Korean Med. Sci. v.14 Effects of interleukin-10 on chemokine KC gene expression by mouse peritoneal macrophages in reponse to Candida albicans Kim, H. S.;D. H. Shin;S. K. Kim https://doi.org/10.3346/jkms.1999.14.5.480
  13. Biochem. Biophys. Res. Commun. v.144 The early competence genes JE and KC are differentially regulated in murine peritoneal macrophages in response to lipopolysaccharide Koerner, T. J.;T. A. Hamilton;M. Introna;C. S. Tannenbaum;R. C. Bast;D. O. Adams, Jr
  14. J. Microbiol. Biotechnol. v.12 Synergistic effect of lipopolysaccharide and interferon-${\beta}$ on the expression of chemokine Mig mRNA Lee, M. S.;S. K. Kim;H. S. Kim
  15. Gastroenterology v.123 Murine leptin deficiency alters kupffer cell procuction of cytokines that regulate the innate immune system Li, Z.;H. Lin;S. Yang;A. M. Diehl https://doi.org/10.1053/gast.2002.35997
  16. FASEB J. v.12 Leptin regulates proinflammatory immune responses Loffreda, S.;S. Q. Yang;H. Z. Lin;C. L. Karp;M. L. Brengman;D. J. Wang;A. S. Klein;G. B. Bulkley;C. Bao;P. W. Noble;M. D. Lane;A. M. Diehl https://doi.org/10.1096/fasebj.12.1.57
  17. Nature v.394 Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression Lord, G. M.;G. Matarese;J. K. Howard;R. J. Baker;S. R. Bloom;R. L. Lechler https://doi.org/10.1038/29795
  18. J. Leukoc. Biol. v.72 Leptin inhibits the anti-CD3-driven proliferation of peripheral blood T cells but enhances the production of proinflammatory cytokines Lord, G. M.;G. Matarese;J. K. Howard;S. R. Bloom;R. I. Lechler
  19. Endocrinology v.139 Leptin signaling in the hypothalamus of normal rats in vivo MaCowne, K. C.;J. C. Chow;R. J. Smith https://doi.org/10.1210/en.139.11.4442
  20. J. Immunol. v.168 Leptin-deficient mice exhibit impaired host defense in gram-negative pneumonia Mancuso, P.;A. Gottschalk;S. M. Phare;M. Peter-Golden;N. W. Lukacs;G. B. Huffnagle https://doi.org/10.4049/jimmunol.168.8.4018
  21. J. Immunol. v.155 Two structurally distint ${\kappa}B$ sequence motifs cooperatively control LPS-induced KC gene transcription in mouse macrophages Ohmori, Y.;S. Fukumoto;T. A. Hamilton
  22. J. Immunol. v.154 IFN-${\gamma}$selectively inhibits lipopolysacharide-inducible JE/monocytes chemoattactant protein-1 and KC/gro/melanoma growth-stimulating activity gene expression in mouse peritoneal macrophages Ohmori, Y.;T. A. Hamilton
  23. Cell. Immunol. v.194 Human leptin stimulates proliferation and activation of human circulating monocytes Santos, A. J.;R. Goberna;M. V. Sanchez https://doi.org/10.1006/cimm.1999.1490
  24. J. Leukoc. Biol. v.72 Acute mast cell-dependent neutrophil recruitment in the skin is mediated by KC and LFA-1: Inhibitory mechanisms of dexamethasone Schramm, R.;T. Schaefer;M. D. Menger;H. Thorlacius
  25. Gastroenterology v.122 Leptin: A pivotal mediator of intestinal inflammation in mice Siegmund, B.;H. A. Lehr;G. Fantuzzi https://doi.org/10.1053/gast.2002.33631
  26. Cell v.83 Identification and expression cloning of a leptin receptor (OB-R) Tartaglia, L. A.;M. Dembski;X. Weng;N. Deng;J. Culpepper;R. Devos;G. J. Richards;L. A. Campfield;K. J. Moore;R. I. Tepper https://doi.org/10.1016/0092-8674(95)90151-5
  27. Nat. Genet. v.14 Leptin activation of Stat3 in the hypothalamus of wild-type ob/ob mice but not db/db mice Vassie, C.;J. L. Halaas;C. M. Horvath;J. E. Darnell Jr.;M. Stoffel;J. M. Friedman https://doi.org/10.1038/ng0996-95
  28. J. Cell. Physiol. v.181 Differential expression and regulation of chemokines JE, KC, and IP-10 gene on primary cultured murine hepatocytes Wang, H;X. Gao;S. Fukumoto;S. Tademoto;K. Sato;K. Hirai https://doi.org/10.1002/(SICI)1097-4652(199911)181:2<361::AID-JCP18>3.0.CO;2-9
  29. Cytokine Growth Factor Rev. v.7 Leptin and OB-R: Body weight regulation by a cytokine receptor White, D. W.;L. A. Tartaglia https://doi.org/10.1016/S1359-6101(96)00040-8
  30. J. Biol. Chem. v.276 Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in arotic endothelial cells by increasing fatty acid oxidation via protein kinase A Yamagishi, S. I.;D. Edelstein;X. L. Du;Y. Kaneda;M. Guzman;M. Brownlee https://doi.org/10.1074/jbc.M007383200
  31. Nature v.372 Positional cloning of the mouse obese gene and its human homologue Zhang, Y.;R. Proenca;M. Maffei;M. Barone;L. Leopold;J. M. Friedman https://doi.org/10.1038/372425a0