IL-1beta-stimulated activation of ERK1/2 and p38alpha MAPK mediates the transcriptional up-regulation of IL-6, IL-8 and GRO-alpha in HeLa cells.
Epithelial cells represent the first line of defense against infection. Here we have studied the production of inflammatory mediators induced by IL-1beta in the HeLa epithelial cell line. We found that GRO-alpha, IL-6 and IL-8 were the only three inflammatory mediators elevated out of 36 tested. Specific inhibition of p38alpha MAP kinase or preventing the activation of ERK1/ERK2 partially reduced the production of these substances, while the combined blockade of both pathways almost abolished secretion. The suppression of these signaling pathways mainly reduced transcription of the genes encoding GRO-alpha, IL-6 and IL-8, rather than affecting mRNA stability, translation or secretion. The production of these three inflammatory mediators was shown to account for the ability of the HeLa cell culture medium to stimulate the migration of monocytes/macrophages, suggesting a key role for p38 MAPK and ERK1/ERK2 in orchestrating the epithelial cell response to infection.
MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Sir James Black Centre, Dow Street, Dundee, DD1 5EH, United Kingdom.
Huei-Ting
HT
Yang
Philip
P
Cohen
Simon
S
Rousseau
D002465:Cell Movement / Q000187:drug effects; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D054360:Chemokine CXCL1; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D017472:Receptors, Interleukin-1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases