Signal transducer and activator of transcription-3 licenses Toll-like receptor 4-dependent interleukin (IL)-6 and IL-8 production via IL-6 receptor-positive feedback in endometrial cells

Mucosal Immunology
James G CroninI Martin Sheldon

Abstract

Interleukin 6 (IL-6), acting via the IL-6 receptor (IL6R) and signal transducer and activator of transcription-3 (STAT3), limits neutrophil recruitment once bacterial infections are resolved. Bovine endometritis is an exemplar mucosal disease, characterized by sustained neutrophil infiltration and elevated IL-6 and IL-8, a neutrophil chemoattractant, following postpartum Gram-negative bacterial infection. The present study examined the impact of the IL6R/STAT3 signaling pathway on IL-8 production by primary endometrial cells in response to short- or long-term exposure to lipopolysaccharide (LPS) from Gram-negative bacteria. Tyrosine phosphorylation of STAT3 is required for DNA binding and expression of specific targets genes. Immunoblotting indicated constitutive tyrosine phosphorylation of STAT3 in endometrial cells was impeded by acute exposure to LPS. After 24 h exposure to LPS, STAT3 returned to a tyrosine phosphorylated state, indicating cross-talk between the Toll-like receptor 4 (TLR4) and the IL6R/STAT3 signaling pathways. This was confirmed by short interfering RNA targeting the IL6R, which abrogated the accumulation of IL-6 and IL-8, induced by LPS. Furthermore, there was a differential endometrial cell response, as t...Continue Reading

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Citations

Jul 15, 2016·Journal of Agricultural and Food Chemistry·Haichong WuGanzhen Deng
Aug 9, 2016·Journal of Reproductive Immunology·Iain Martin SheldonMatthew Lloyd Turner
Jan 16, 2020·Environmental Health Perspectives·Pierre-André LafonVéronique Perrier
Apr 20, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yunjuan NiePeng Zhao

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Methods Mentioned

BETA
co-immunoprecipitation
immunoprecipitation
fluorescence-activated cell sorting
FACS
ELISA
Assay
transfections
PCR

Software Mentioned

SPSS
BD
Quantity
one
qBase
Stattic
FACSDiva

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