Cyclosporin A does not inhibit IL-1 alpha-induced epithelial cell IL-6 secretion.
Trauma and infection activated a murine mucosal IL-6 response in different ways: the IL-6 response to bacteria was sensitive to Cyclosporin A (CsA); the IL-6 response to trauma was not. The aim of the present study was to identify possible activators of the CsA-insensitive IL-6 secretion at the epithelial cell level. Two human epithelial cell lines from the kidney (A498) and bladder (J82) were exposed to Escherichia coli Hu734, interleukin-1 alpha (IL-1 alpha) and tumour necrosis factor alpha (TNF-alpha). The E. coli strain had been used for the in vivo experiments which led to this study, and IL-1 alpha and TNF-alpha were likely to be released during infections and trauma. The secretion of IL-6 into the supernatants was compared between cells stimulated in the presence or absence of CsA. E. coli Hu734, IL-1 alpha and TNF-alpha stimulated an IL-6 response in the two epithelial cell lines. The IL-1 alpha-induced IL-6 response was rapid, and the secreted IL-6 levels were significantly higher than those induced by E. coli Hu734 or TNF-alpha. The IL-6 response to IL-1 alpha was insensitive to CsA. By contrast, the IL-6 response to E. coli Hu734 and TNF-alpha was inhibited by CsA. These results demonstrated that the inhibitory effect of CsA depends on the stimulus triggering the IL-6 response. IL-1 alpha may play a role in the induction of trauma-associated CsA-insensitive IL-6 secretion.
Hedges
S
S
Department of Clinical Immunology, University of Lund, Sweden.
Agace
W
W
Svensson
M
M
Svanborg
C
C
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D004848:Epithelium / Q000187:drug effects / Q000276:immunology; D007375:Interleukin-1 / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine