Differential Expression of the Activator Protein 1 Transcription Factor Regulates Interleukin-1ß Induction of Interleukin 6 in the Developing Enterocyte

PloS One
Catherine M CahillW Allan Walker

Abstract

The innate immune response is characterized by activation of transcription factors, nuclear factor kappa B and activator protein-1 and their downstream targets, the pro-inflammatory cytokines including interleukin 1β and interleukin 6. Normal development of this response in the intestine is critical to survival of the human neonate and delays can cause the onset of devastating inflammatory diseases such as necrotizing enterocolitis. Previous studies have addressed the role of nuclear factor kappa B in the development of the innate immune response in the enterocyte, however despite its central role in the control of multiple pro-inflammatory cytokine genes, little is known on the role of Activator Protein 1 in this response in the enterocyte. Here we show that the canonical Activator Protein 1 members, cJun and cFos and their upstream kinases JNK and p38 play an essential role in the regulation of interleukin 6 in the immature enterocyte. Our data supports a model whereby the cFos/cJun heterodimer and the more potent cJun homodimer downstream of JNK are replaced by less efficient JunD containing dimers, contributing to the decreased responsiveness to interleukin 1β and decreased interleukin 6 secretion observed in the mature ent...Continue Reading

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Citations

Aug 27, 2016·American Journal of Physiology. Gastrointestinal and Liver Physiology·Di MengW Allan Walker
Nov 6, 2018·Current Pediatric Reviews·Catalina Bazacliu, Josef Neu
Apr 21, 2019·International Journal of Molecular Sciences·Kathryn BurgeHala Chaaban

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Methods Mentioned

BETA
xenograft
xenografts
ELISA
Protein assay
transfection
electrophoretic mobility shift assay

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