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IL-1 signaling mediates intrauterine inflammation and chorio-decidua neutrophil recruitment and activation
Pietro Presicce, … , Alan H. Jobe, Suhas G. Kallapur
Pietro Presicce, … , Alan H. Jobe, Suhas G. Kallapur
Published March 22, 2018
Citation Information: JCI Insight. 2018;3(6):e98306. https://doi.org/10.1172/jci.insight.98306.
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Research Article Immunology Reproductive biology

IL-1 signaling mediates intrauterine inflammation and chorio-decidua neutrophil recruitment and activation

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Abstract

Neutrophil infiltration of the chorioamnion-decidua tissue at the maternal-fetal interface (chorioamnionitis) is a leading cause of prematurity, fetal inflammation, and perinatal mortality. We induced chorioamnionitis in preterm rhesus macaques by intraamniotic injection of LPS. Here, we show that, during chorioamnionitis, the amnion upregulated phospho-IRAK1–expressed neutrophil chemoattractants CXCL8 and CSF3 in an IL-1–dependent manner. IL-1R blockade decreased chorio-decidua neutrophil accumulation, neutrophil activation, and IL-6 and prostaglandin E2 concentrations in the amniotic fluid. Neutrophils accumulating in the chorio-decidua had increased survival mediated by BCL2A1, and IL-1R blockade also decreased BCL2A1+ chorio-decidua neutrophils. Readouts for inflammation in a cohort of women with preterm delivery and chorioamnionitis were similar to findings in the rhesus macaques. IL-1 is a potential therapeutic target for chorioamnionitis and associated morbidities.

Authors

Pietro Presicce, Chan-Wook Park, Paranthaman Senthamaraikannan, Sandip Bhattacharyya, Courtney Jackson, Fansheng Kong, Cesar M. Rueda, Emily DeFranco, Lisa A. Miller, David A. Hildeman, Nathan Salomonis, Claire A. Chougnet, Alan H. Jobe, Suhas G. Kallapur

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Figure 2

Activation of IRAK1 and induction of neutrophil chemoattractants is IL-1 dependent in the amnion.

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Activation of IRAK1 and induction of neutrophil chemoattractants is IL-1...
Amnion was physically separated from chorion and decidua immediately after birth from rhesus and humans delivering preterm. (A) Representative immunoblots of rhesus amnion (n = 5) probed with anti–phospho-IRAK1 and β-actin and quantification of IRAK1 expression (Ctrl, n = 4; LPS, n = 6; LPS + rhIL-1ra, n = 4) are shown. (B) Expression of IA LPS–induced CSF3, IL8/CXCL8, and IL6 but not IL1β mRNA were inhibited by rhIL-1ra (Ctrl, n = 13; LPS, n = 11; LPS + rhIL-1ra, n = 6). (C) Representative immunoblots of human amnion (n = 5) probed with anti–phospho-IRAK1 and β-actin and quantification of IRAK1 expression (Chorio neg., n = 4; Chorio pos., n = 6) are shown. (D) CSF3, IL8, IL6, and IL1β mRNAs increased in human chorio cases (Chorio neg., n = 16; Chorio pos., n = 11). (E) Model demonstrating IL-1β downstream of TLR and CXCL8/CSF3 downstream of IL-1R in the amnion. Data are mean ± SEM, *P < 0.05 between comparators by Mann-Whitney test.

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