Download PDF
Horm Metab Res 2014; 46(06): 384-389
DOI: 10.1055/s-0034-1368710
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Leptin does not Induce an Inflammatory Response in the Murine Placenta

S. Appel   *
1   Department of Paediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany
,
E-M. Turnwald   *
1   Department of Paediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany
,
M. A. Alejandre-Alcazar
1   Department of Paediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany
,
J. Ankerne
1   Department of Paediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany
,
E. Rother
1   Department of Paediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany
,
R. Janoschek
1   Department of Paediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany
,
M. Wohlfarth
1   Department of Paediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany
,
C. Vohlen
1   Department of Paediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany
,
M. Schnare
2   Institute for Immunology, University of Marburg, Marburg, Germany
,
U. Meißner
3   Hainstrasse 20, Bamberg, Germany
,
J. Dötsch
1   Department of Paediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany
› Author Affiliations
Further Information

Publication History

received 26 September 2013

accepted 29 January 2014

Publication Date:
03 March 2014 (online)

Also available at
    Permissions and Reprints

Abstract

Leptin is described as a pro-inflammatory signal in fat tissue, which is released from adipocytes and in turn activates immune cells. Also, leptin levels are known to be increased in pregnancies complicated with enhanced inflammatory processes in the placenta. Hence, we assumed that increased leptin amounts might contribute to inducing an inflammatory response in the placenta. To test this hypothesis, pregnant mice were continuously infused with recombinant murine leptin s. c. from day g13 to g16, resulting in a 3-fold increase of maternal circulating serum leptin levels. Dissected placentas were examined for the expression of pro-inflammatory cytokines IL-6 and TNF-alpha and the anti-inflammatory cytokine IL-10 using qPCR analysis. No changes were found except for TNF-alpha, which was slightly elevated upon leptin stimulation. However, TNF-alpha protein levels were not significantly higher in placentas from leptin treated mice. Also, leukocyte infiltration in the labyrinth section of placentas was not increased. In summary, our data demonstrate for the first time that elevated leptin levels alone do not induce an inflammatory response in the placenta.

Key words

placenta - inflammation - leptin

* These authors contributed equally to this work.


 

  • References

  • 1 Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS. Role of leptin in the neuroendocrine response to fasting. Nature 1996; 382: 250-252
    CrossrefPubMedSearch in Google Scholar
  • 2 Cinti S, Frederich RC, Zingaretti MC, De Matteis R, Flier JS, Lowell BB. Immunohistochemical localization of leptin and uncoupling protein in white and brown adipose tissue. Endocrinology 1997; 138: 797-804
    CrossrefPubMedSearch in Google Scholar
  • 3 Masuyama H, Nakatsukasa H, Takamoto N, Hiramatsu Y. Correlation between soluble endoglin, vascular endothelial growth factor receptor-1, and adipocytokines in preeclampsia. J Clin Endocrinol Metab 2007; 92: 2672-2679
    CrossrefPubMedSearch in Google Scholar
  • 4 Niswender KD, Schwartz MW. Insulin and leptin revisited: adi­posity signals with overlapping physiological and intracellular signaling capabilities. Front Neuroendocrinol 2003; 24: 1-10
    CrossrefPubMedSearch in Google Scholar
  • 5 La Cava A, Matarese G. The weight of leptin in immunity. Nat Rev Immunol 2004; 4: 371-379
    CrossrefPubMedSearch in Google Scholar
  • 6 Bowen JM, Chamley L, Mitchell MD, Keelan JA. Cytokines of the placenta and extra-placental membranes: biosynthesis, secretion and roles in establishment of pregnancy in women. Placenta 2002; 23: 239-256
    CrossrefPubMedSearch in Google Scholar
  • 7 Challier JC, Basu S, Bintein T, Minium J, Hotmire K, Catalano PM, Hauguel-de Mouzon S. Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta. Placenta 2008; 29: 274-281
    CrossrefPubMedSearch in Google Scholar
  • 8 Radaelli T, Varastehpour A, Catalano P, Hauguel-de Mouzon S. Gestational diabetes induces placental genes for chronic stress and inflammatory pathways. Diabetes 2003; 52: 2951-2958
    CrossrefPubMedSearch in Google Scholar
  • 9 Rusterholz C, Hahn S, Holzgreve W. Role of placentally produced inflammatory and regulatory cytokines in pregnancy and the etiology of preeclampsia. Semin Immunopathol 2007; 29: 151-162
    CrossrefPubMedSearch in Google Scholar
  • 10 Enquobahrie DA, Meller M, Rice K, Psaty BM, Siscovick DS, Williams MA. Differential placental gene expression in preeclampsia. Am J Obstet Gynecol 2008; 199: 566-e561–e511
    PubMedSearch in Google Scholar
  • 11 Dotsch J, Nusken KD, Knerr I, Kirschbaum M, Repp R, Rascher W. Leptin and neuropeptide Y gene expression in human placenta: ontogeny and evidence for similarities to hypothalamic regulation. J Clin Endocrinol Metab 1999; 84: 2755-2758
    CrossrefPubMedSearch in Google Scholar
  • 12 Hendler I, Blackwell SC, Mehta SH, Whitty JE, Russell E, Sorokin Y, Cotton DB. The levels of leptin, adiponectin, and resistin in normal weight, overweight, and obese pregnant women with and without preeclampsia. Am J Obstet Gynecol 2005; 193: 979-983
    CrossrefPubMedSearch in Google Scholar
  • 13 Cameo P, Bischof P, Calvo JC. Effect of leptin on progesterone, human chorionic gonadotropin, and interleukin-6 secretion by human term trophoblast cells in culture. Biol Reprod 2003; 68: 472-477
    PubMedSearch in Google Scholar
  • 14 Rother E, Kuschewski R, Alcazar MA, Oberthuer A, Bae-Gartz I, Vohlen C, Roth B, Dotsch J. Hypothalamic JNK1 and IKKbeta activation and impaired early postnatal glucose metabolism after maternal perinatal high-fat feeding. Endocrinology 2012; 153: 770-781
    CrossrefPubMedSearch in Google Scholar
  • 15 Hegen M, Gaestel M, Nickerson-Nutter CL, Lin LL, Telliez JB. MAPKAP kinase 2-deficient mice are resistant to collagen-induced arthritis. J Immunol 2006; 177: 1913-1917
    CrossrefPubMedSearch in Google Scholar
  • 16 Yang J, Rosen SD, Bendele P, Hemmerich S. Induction of PNAd and N-acetylglucosamine 6-O-sulfotransferases 1 and 2 in mouse collagen-induced arthritis. BMC Immunol 2006; 7: 12
    CrossrefPubMedSearch in Google Scholar
  • 17 Sucak A, Kanat-Pektas M, Gungor T, Mollamahmutoglu L. Leptin levels and antihypertensive treatment in preeclampsia. Singapore Med J 2010; 51: 39-43
    PubMedSearch in Google Scholar
  • 18 Anim-Nyame N, Sooranna SR, Steer PJ, Johnson MR. Longitudinal analysis of maternal plasma leptin concentrations during normal pregnancy and pre-eclampsia. Hum Reprod 2000; 15: 2033-2036
    CrossrefPubMedSearch in Google Scholar
  • 19 Mumtaz F, Memon AR, Yousfani S, Tahir SM, Khushk I, Memon M, Memon A. Role of serum leptin level as a marker of severity of pre eclampsia. J Ayub Med Coll Abbottabad 2008; 20: 13-15
    PubMedSearch in Google Scholar
  • 20 Ramsay JE, Ferrell WR, Crawford L, Wallace AM, Greer IA, Sattar N. Maternal obesity is associated with dysregulation of metabolic, vascular, and inflammatory pathways. J Clin Endocrinol Metab 2002; 87: 4231-4237
    CrossrefPubMedSearch in Google Scholar
  • 21 Castellucci M, De Matteis R, Meisser A, Cancello R, Monsurro V, Islami D, Sarzani R, Marzioni D, Cinti S, Bischof P. Leptin modulates extracellular matrix molecules and metalloproteinases: possible implications for trophoblast invasion. Mol Hum Reprod 2000; 6: 951-958
    CrossrefPubMedSearch in Google Scholar
  • 22 Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J, Muir C, Sanker S, Moriarty A, Moore KJ, Smutko JS, Mays GG, Wool EA, Monroe CA, Tepper RI. Identification and expression cloning of a leptin receptor. OB-R. Cell 1995; 83: 1263-1271
    PubMedSearch in Google Scholar
  • 23 Chehab FF, Lim ME, Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet 1996; 12: 318-320
    CrossrefPubMedSearch in Google Scholar
  • 24 Sierra-Honigmann MR, Nath AK, Murakami C, Garcia-Cardena G, Papapetropoulos A, Sessa WC, Madge LA, Schechner JS, Schwabb MB, Polverini PJ, Flores-Riveros JR. Biological action of leptin as an angiogenic factor. Science 1998; 281: 1683-1686
    CrossrefPubMedSearch in Google Scholar
  • 25 Jansson N, Greenwood SL, Johansson BR, Powell TL, Jansson T. Leptin stimulates the activity of the system A amino acid transporter in human placental villous fragments. J Clin Endocrinol Metab 2003; 88: 1205-1211
    CrossrefPubMedSearch in Google Scholar
  • 26 Bowen RS, Gu Y, Zhang Y, Lewis DF, Wang Y. Hypoxia promotes interleukin-6 and -8 but reduces interleukin-10 production by placental trophoblast cells from preeclamptic pregnancies. J Soc Gynecol Investig 2005; 12: 428-432
    CrossrefPubMedSearch in Google Scholar
  • 27 McDonald EA, Kurtis JD, Acosta L, Gundogan F, Sharma S, Pond-Tor S, Wu HW, Friedman JF. Schistosome egg antigens elicit a proinflammatory response by trophoblast cells of the human placenta. Infect Immun 2013; 81: 704-712
    CrossrefPubMedSearch in Google Scholar
  • 28 Noyola-Martinez N, Diaz L, Avila E, Halhali A, Larrea F, Barrera D. Calcitriol downregulates TNF-alpha and IL-6 expression in cultured placental cells from preeclamptic women. Cytokine 2013; 61: 245-250
    CrossrefPubMedSearch in Google Scholar
  • 29 Klaffenbach D, Meissner U, Raake M, Fahlbusch F, Alejandre Alcazar MA, Allabauer I, Kratzsch J, Rascher W, Dotsch J. Upregulation of leptin-receptor in placental cells by hypoxia. Regul Pept 2011; 167: 156-162
    CrossrefPubMedSearch in Google Scholar
  • 30 Schulz LC, Widmaier EP, Qiu J, Roberts RM. Effect of leptin on mouse trophoblast giant cells. Biol Reprod 2009; 80: 415-424
    PubMedSearch in Google Scholar
  • 31 Schulz LC, Widmaier EP. The effect of leptin on mouse trophoblast cell invasion. Biol Reprod 2004; 71: 1963-1967
    CrossrefPubMedSearch in Google Scholar