Probiotics regulate the expression of COX-2 in intestinal epithelial cells.
Cyclooxygenase-2 (COX) 2 promotes intestinal wound healing but elicits also proinflammatory effects and has been implicated in colorectal carcinogenesis. Thus, a balanced expression of COX-2 is essential for intestinal homeostasis. This study was designed to evaluate the regulation of COX-2 by probiotic organisms and to characterize ligands and receptors involved. Colo320 and SW480 intestinal epithelial cells (IEC) were stimulated with gastrin or TNF-alpha and pre- or coincubated with commensales, bacterial supernatants, or distinct toll-like receptor (TLR) ligands. COX-2 promoter activity was determined by luciferase assays, protein expression by Western blotting, and secretion of prostaglandin E(2) (PGE(2)) by ELISA. Commensales differentially regulated COX-2 expression in IEC. E. coli Nissle 1917, the probiotic mixture VSL#3, and media conditioned by these organisms ameliorated induced COX-2 expression and PGE(2) secretion. Heat inactivation and DNase treatment significantly decreased these regulatory capacities. Lactobacillus acidophilus, however, significantly increased COX-2 expression and PGE(2) secretion. TLR agonists differentially ameliorated basal or induced COX-2 expression. Distinct probiotics specifically and significantly decrease induced COX-2 expression in IEC, most likely mediated by released factors and in part by bacterial DNA. A significant involvement of TLRs in these regulatory processes remains to be established.
Otte
Jan-Michel
JM
Department of Internal Medicine I, St. Josef-Hospital, Ruhr-University, Bochum, Germany. jan-michel.otte@rub.de
Mahjurian-Namari
Rudja
R
Brand
Stephan
S
Werner
Ilka
I
Schmidt
Wolfgang E
WE
Schmitz
Frank
F
D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000382:microbiology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004847:Epithelial Cells / Q000201:enzymology / Q000382:microbiology; D004926:Escherichia coli / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D007779:Lactobacillus acidophilus / Q000502:physiology*; D008024:Ligands; D019936:Probiotics / Q000494:pharmacology*; D015398:Signal Transduction; D013045:Species Specificity; D051193:Toll-Like Receptors / Q000378:metabolism
D008024:Ligands; D051193:Toll-Like Receptors; D051546:Cyclooxygenase 2