An M1-like macrophage polarization in decidual tissue during spontaneous preterm labor that is attenuated by rosiglitazone treatment

Yi Xu, Roberto Romero, Derek Miller, Leena Kadam, Tara N. Mial, Olesya Plazyo, Valeria Garcia-Flores, Sonia S. Hassan, Zhonghui Xu, Adi L. Tarca, Sascha Drewlo, Nardhy Gomez-Lopez

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

Decidual macrophages are implicated in the local inflammatory response that accompanies spontaneous pretermlabor/birth; however, their role is poorly understood. We hypothesized that decidual macrophages undergo a proinflammatory (M1) polarization during spontaneous preterm labor and that PPARγ activation via rosiglitazone (RSG) would attenuate the macrophage-mediated inflammatory response, preventing preterm birth. In this study, we show that: 1) decidual macrophages undergo an M1-like polarization during spontaneous term and preterm labor; 2) anti-inflammatory (M2)-like macrophages are more abundant than M1-like macrophages in decidual tissue; 3) decidual M2-like macrophages are reduced in preterm pregnancies compared with term pregnancies, regardless of the presence of labor; 4) decidual macrophages express high levels of TNF and IL-12 but low levels of peroxisome proliferator-activated receptor g (PPARγ) during spontaneous preterm labor; 5) decidual macrophages from women who underwent spontaneous preterm labor display plasticity by M1虠M2 polarization in vitro; 6) incubation with RSG reduces the expression of TNF and IL-12 in decidual macrophages from women who underwent spontaneous preterm labor; and 7) treatment with RSG reduces the rate of LPS-induced preterm birth and improves neonatal outcomes by reducing the systemic proinflammatory response and downregulating mRNA and protein expression of NF-κB, TNF, and IL-10 in decidual and myometrial macrophages in C57BL/6J mice. In summary, we demonstrated that decidual M1-like macrophages are associated with spontaneous preterm labor and that PPARγ activation via RSG can attenuate the macrophage-mediated proinflammatory response, preventing preterm birth and improving neonatal outcomes. These findings suggest that the PPARγ pathway is a new molecular target for future preventative strategies for spontaneous preterm labor/birth.

Original languageEnglish (US)
Pages (from-to)2476-2491
Number of pages16
JournalJournal of Immunology
Volume196
Issue number6
DOIs
StatePublished - Mar 15 2016
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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