title: Antioxidants counteract lipopolysaccharide-triggered alterations of human colonic smooth muscle cells.
abstract: Gut dysmotility develops in individuals during and after recovering from infective acute gastroenteritis and it is apparently due to a direct effect of circulating lipopolysaccharides (LPS). This is an endotoxin with a prooxidant activity derived from gram-negative bacteria. Due to the lack of human models available so far, the mechanisms underlying LPS-induced gut dysmotility are, however, poorly investigated. In the present work long-term effects of LPS and their reversibility have been assessed by means of different analytical cytology methods on pure primary cultures of human colonic smooth muscle cells. We found that LPS triggered the following alterations: (i) a redox imbalance with profound changes of contractile microfilament network, and (ii) the induction of cell cycle progression with dedifferentiation from a contractile to a synthetic phenotype. These alterations persisted also after LPS removal. Importantly, two unrelated antioxidants, alpha-tocopherol and N-acetylcysteine, were able to reverse the cytopathic effects of LPS and to restore normal muscle cell function. The present data indicate that LPS is capable of triggering a persistent and long-term response that could contribute to muscle dysfunction occurring after an infective and related inflammatory burst and suggest a reappraisal of antioxidants in the management of postinfective motor disorders of the gut.
authors.affiliation: Department of Drug Research and Evaluation, Istituto Superiore di Sanità, Rome, Italy. paola.matarrese@iss.it
authors.forename: Paola
authors.initials: P
authors.lastname: Matarrese
authors.forename: Chiara
authors.initials: C
authors.lastname: Petitta
authors.forename: Annunziata
authors.initials: A
authors.lastname: Scirocco
authors.forename: Barbara
authors.initials: B
authors.lastname: Ascione
authors.forename: Francesca
authors.initials: F
authors.lastname: Ammoscato
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Natale
authors.forename: Emanuela
authors.initials: E
authors.lastname: Anastasi
authors.forename: Matteo
authors.initials: M
authors.lastname: Marconi
authors.forename: Piero
authors.initials: P
authors.lastname: Chirletti
authors.forename: Walter
authors.initials: W
authors.lastname: Malorni
authors.forename: Carola
authors.initials: C
authors.lastname: Severi
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology*; D005260:Female; D005452:Fluoresceins; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D010042:Ouabain / Q000031:analogs & derivatives; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D005452:Fluoresceins; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; C109049:rhodol green-ethylenediamine-ouabain; D016753:Interleukin-10; D010042:Ouabain; D024502:alpha-Tocopherol; D000111:Acetylcysteine