Reduced intestinal epithelial mitochondrial function enhances in vitro interleukin-8 production in response to commensal Escherichia coli

Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]
Alpana SaxenaDerek M McKay

Abstract

Uncoupling of oxidative phosphorylation in epithelial mitochondria results in decreased epithelial barrier function as characterized by increased internalization of non-invasive Escherichia coli and their translocation across the epithelium. We hypothesized that the increased burden of intracellular commensal bacteria would activate the enterocyte, with the potential to promote inflammation. Treatment of human colon-derived epithelial cell lines in vitro with dinitrophenol (DNP) and commensal E. coli (strains F18, HB101) provoked increased production of interleukin (IL-8), which was not observed with conditioned medium from the bacteria, lipopolysaccharide or inert beads. The IL-8 response was inhibited by co-treatment with cytochalasin-D (blocks F-actin rearrangement), chloroquine (blocks phagosome acidification) and a MyD88 inhibitor (blocks TLR signaling), consistent with TLR-signaling mediating IL-8 synthesis subsequent to bacterial internalization. Use of the mitochondria-targeted antioxidant, mitoTEMPO, or U0126 to block ERK1/2 MAPK signalling inhibited DNP+E. coli-evoked IL-8 production. Mutations in the NOD2 (the intracellular sensor of bacteria) or ATG16L1 (autophagy protein) genes are susceptibility traits for Crohn's...Continue Reading

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Citations

Apr 24, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Viviani MendesAngelica Thomaz Vieira
Mar 3, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Derek M McKayTimothy Shutt
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Wen XiongZili Wang
Aug 3, 2021·Journal of Immunology Research·Shunyu YaoXiaolu Liu
Apr 23, 2019·European Journal of Pharmacology·Anna HerminghausRichard Truse

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Methods Mentioned

BETA
biopsies
ELISA
Assay

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