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Inamm. Res. (2014) 63:179189DOI 10.1007/s00011-013-0687-z Inammation Research
ORIGINAL RESEARCH PAPER
CX3CL1 (fractalkine) and TNFa production by perfused human placental lobules under normoxic and hypoxic conditions in vitro: the importance of CX3CR1 signaling
Dariusz Szukiewicz Jan Kochanowski Tarun Kumar Mittal
Michal Pyzlak Grzegorz Szewczyk Krzysztof Cendrowski
Received: 10 April 2013 / Revised: 3 October 2013 / Accepted: 6 November 2013 / Published online: 24 November 2013 The Author(s) 2013. This article is published with open access at Springerlink.com
AbstractObjective Inammation and hypoxia activate the fractalkine (CX3CL1) receptor (CX3CR1)-related signaling pathway. Tumor necrosis factor alpha (TNFa) induces
CX3CL1, inuencing a mechanism of CX3CL1 autoregulation by CX3CR1 expression. We compared spontaneous and lipopolysaccharide (LPS)-induced CX3CL1 and TNFa production by human placenta under normoxic vs. hypoxic conditions, with respect to CX3CR1 expression and its functional status.
Methods Placental lobules of term placentae (N = 24) were perfused extracorporeally. CX3CL1 and TNFa concentrations were measured in the perfusion uid by ELISA. LPS, anti-CX3CR1 antibodies and pirfenidone were used in respective subgroups. After perfusion, CX3CR1 expression was estimated in placental tissue using quantitative immunohistochemistry, and the nal results were adjusted for the mean microvascular density.
Results The highest increase in CX3CL1 concentration in response to LPS was observed in hypoxia (p \ 0.05).
Unlike in normoxia, anti-CX3CR1 administration in hypoxia signicantly reduced the LPS-evoked response. CX3CR1 expression was augmented by hypoxia and reached 260.9 41 (% SEM) of the reference value in normoxia. Positive immunostaining for CX3CR1 corresponded to the vascular endothelium. Pirfenidone inhibited hypoxia ? LPS-related increase in TNFa production and prevented the up-regulation of CX3CR1.
Conclusion The modulatory inuence of TNFa on
CX3CR1 expression in hypoxia and CX3CL1/CX3CR1 interaction may serve as a compensatory mechanism to preserve or augment the pro-inammatory course of intercellular interactions in placental endothelium.
Keywords Fractalkine/CX3CR1 TNFa
Human placenta In vitro perfusion study Hypoxia
CX3CR1 expression
Introduction
Because placental vessels lack autonomic innervation, circulating and locally produced humoral factors must play a crucial role in communication between the compartments of the utero-placento-fetal unit [1]. In addition to vascular
Responsible Editor: Liwu Li.
D. Szukiewicz (&) M. Pyzlak G. Szewczyk
Department of General and Experimental Pathology, Second Faculty of Medicine, Medical University of Warsaw, ul. Krakowskie Przedmiescie 26/28, 00-928 Warsaw, Poland e-mail: [email protected]
M. Pyzlake-mail: [email protected]