Exposure of Toll-like receptors 4 to bacterial lipopolysaccharide (LPS) impairs human colonic smooth muscle cell function

J Cell Physiol. 2010 May;223(2):442-50. doi: 10.1002/jcp.22053.


Endotoxemia by bacterial lipopolysaccharide (LPS) has been reported to affect gut motility specifically depending on Toll-like receptor 4 activation (TLR4). However, the direct impact of LPS ligation to TLR4 on human smooth muscle cells (HSMC) activity still remains to be elucidated. The present study shows that TLR4, its associated molecule MD2, and TLR2 are constitutively expressed on cultured HSMC and that, once activated, they impair HSMC function. The stimulation of TLR4 by LPS induced a time- and dose-dependent contractile dysfunction, which was associated with a decrease of TLR2 messenger, a rearrangement of microfilament cytoskeleton and an oxidative imbalance, i.e., the formation of reactive oxygen species (ROS) together with the depletion of GSH content. An alteration of mitochondria, namely a hyperpolarization of their membrane potential, was also detected. Most of these effects were partially prevented by the NADPH oxidase inhibitor apocynin or the NFkappaB inhibitor MG132. Finally, a 24 h washout in LPS-free medium almost completely restored morphofunctional and biochemical HSMC resting parameters, even if GSH levels remained significantly lower and no recovery was observed in TLR2 expression. Thus, the exposure to bacterial endotoxin directly and persistently impaired gastrointestinal smooth muscle activity indicating that HSMC actively participate to dysmotility during infective burst. The knowledge of these interactions might provide novel information on the pathogenesis of infection-associated gut dysmotility and further clues for the development of new therapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Colitis / complications*
  • Colitis / physiopathology
  • Colon / cytology
  • Colon / metabolism*
  • Colon / physiopathology
  • Dose-Response Relationship, Drug
  • Endotoxemia / chemically induced
  • Endotoxemia / physiopathology
  • Gastrointestinal Motility / drug effects
  • Gastrointestinal Motility / physiology*
  • Humans
  • Ileus / microbiology*
  • Ileus / physiopathology
  • Inflammation Mediators / pharmacology
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Antigen 96 / drug effects
  • Lymphocyte Antigen 96 / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Potential, Mitochondrial / physiology
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Toll-Like Receptor 2 / drug effects
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / drug effects
  • Toll-Like Receptor 4 / metabolism*


  • Inflammation Mediators
  • LY96 protein, human
  • Lipopolysaccharides
  • Lymphocyte Antigen 96
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4