Cellular strain amplifies LPS-induced stress signaling in immature enterocytes: potential implications for preterm infant NCPAP.
BACKGROUND
Recent clinical observations of increased necrotizing enterocolitis (NEC) incidence in some nasal continuous positive airway pressure (NCPAP) patients raise concerns about whether the related abdominal distension is benign or contributes to NEC. We tested the hypothesis that mechanical strain causes an exaggerated enterocyte inflammatory response and decreased enterocyte growth and proliferation in the absence and presence of lipopolysaccharide (LPS).


METHODS
First we used a confluent enterocyte (IEC-6) monolayer to investigate effects of strain on inflammatory cytokine production and Toll-like receptor 4 (TLR-4) gene expression. Then we used a low seeding density to measure cell growth and proliferation. Ten percent mechanical strain was applied.


RESULTS
Significant increases in interleukin (IL)-8 and in IL-6 were observed after 8 and 24 h of cellular strain, respectively, and maintained throughout the study. TLR-4 expression was increased at 48 h. Mechanical strain led to slower proliferation and division whereas LPS alone had minimal effects. The responses of LPS and strain were supra-additive, suggesting synergistic cellular effects.


CONCLUSIONS
We speculate intestinal distension associated with the use of NCPAP, especially in the presence of abnormal gut colonization, may result in increased inflammatory cytokine production and be a contributing factor to neonatal intestinal morbidities.
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Alicia M
AM
Alcamo
Brandon L
BL
Schanbacher
Hong
H
Huang
Craig A
CA
Nankervis
John A
JA
Bauer
Peter J
PJ
Giannone
D049109:Cell Proliferation / Q000187:drug effects; D045422:Continuous Positive Airway Pressure; D020895:Enterocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4