Osmotic stress, a proinflammatory signal in Caco-2 cells.
Hyper- (450 mOsm/l) and hypoosmotic exposure (150 mOsm/l) of Caco-2 cells, a human intestinal epithelial cell line, induced a twofold- and a fivefold increase in the production of IL-8, a constitutively expressed cytokine, respectively. This was observed both in the presence or in the absence of added proinflammatory cytokines and the stimulatory effect of osmotic stress was additive to that induced by the cytokines. Thus, IL-8 production appeared minimal around isoosmolarity, i.e. 300 mOsm/l. Concerning the signalling pathway involved, specific inhibition of p38- or p42/44 MAP kinases decreased the IL-8 production by about 30% independently of the osmotic condition used. Inhibition of c-jun-NH2-terminal kinase (JNK) by using both dicoumarol and SP600125 totally inhibited the stimulatory effect of hypoosmolarity. Moreover, hypoosmolarity induced an about threefold increase in JNK activity demonstrating that JNK was specifically involved in the effect of hypoosmolarity on IL-8 production. This is not the case for hyperosmolarity. Such an effect of osmotic stress was not restricted to IL-8, but was also observed on the production of IL-6, a non-constitutively expressed cytokine. Again, IL-6 production appeared minimal in isoosmotic condition. Taken together, these results demonstrate that osmotic stress is a proinflammatory signal in Caco-2 cells and suggest that an osmosensor might specifically exist in intestinal epithelial cells.
Hubert
Aurélie
A
ADEN, EA-3234, IFR-23, UFR Médecine-Pharmacie de Rouen, 22, bd Gambetta, 76183 Rouen, France.
Cauliez
Bruno
B
Chedeville
Arlette
A
Husson
Annie
A
Lavoinne
Alain
A
D015415:Biomarkers / Q000032:analysis; D018938:Caco-2 Cells; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009997:Osmotic Pressure / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D015415:Biomarkers; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases