Cytokine-induced impairment of short-chain fatty acid oxidation and viability in human colonic epithelial cells.
Pro-inflammatory cytokines may directly influence the viability and metabolic function of colonic epithelial cells (CEC) as an early event in the development of inflammatory bowel disease. We report here that TNF-alpha+IFN-gamma induced a synergistic, concentration-dependent decline in butyrate oxidation, an essential energy supply, in HT-29 and DLD-1 cells. TNF-alpha+IFN-gamma induced a parallel profound decline in cell viability in HT-29 cells, but not in DLD-1 cells, where impairment of butyrate oxidation seemed to precede later occurrence of cell damage. TNF-alpha+INF-gamma induced CEC damage was independent on NO formation and involved the IFN-gamma signalling pathway as well as induction of apoptosis. If cytokines have similar effects in vivo, these may lead to energy deficiency and thus contribute to CEC damage and disturbance of the epithelial integrity.
Pedersen
G
G
Department of Gastroenterology C, Herlev Hospital, University of Copenhagen, DK-2720 Herlev, Denmark. giped@herlehosp.kbhamt.dk
Saermark
T
T
Horn
T
T
Giese
B
B
Bendtzen
K
K
Brynskov
J
J
D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003106:Colon / Q000378:metabolism*; D004396:Coloring Agents / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008854:Microscopy, Electron; D009569:Nitric Oxide / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002087:Butyrates; D004396:Coloring Agents; D016207:Cytokines; D005232:Fatty Acids, Volatile; D007375:Interleukin-1; D011994:Recombinant Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D002245:Carbon Dioxide; D009569:Nitric Oxide; D007371:Interferon-gamma; C022616:thiazolyl blue; D010100:Oxygen