Modulation of cytokine-induced production of IL-8 in vitro by interferons and glucocorticosteroids.
Interleukin-8 (IL-8) has been implicated in the pathogenesis of inflammation and cancer. Intracellular levels of cytokine-induced IL-8 in human umbilical vein endothelial cells (HUVEC) were modulated using interferons and steroids to further elucidate their mechanism. Basal and cytokine-induced production of IL-8 was studied using a novel ELISA application, flow cytometry, and RT-PCR. The intracellular amount of IL-8 increased after 6-h stimulation with TNF-alpha (30%) or IL-1beta (55%) which was doubled when Golgi transport was disrupted using monensin. IFN-gamma decreased the intracellular amount of IL-8 by 60% in both unstimulated and TNF-alpha-stimulated cells, but only when secretion was blocked using monensin. Dexamethasone inhibited the TNF-alpha-induced production by 33%, but had no effect in unstimulated cells. Our study indicated that both, dexamethasone and IFN inhibit TNF-alpha-induced upregulation of IL-8 at the mRNA level. It could be speculated that they inhibit IL-8 production by affecting different gene regulatory mechanisms.
Nyhlén
Kristina
K
Division of Pharmacology, Department of Medicine and Care, Faculty of Health Science, Linköping, Sweden. kristina.nyhlen@bcrc.nu
Gautam
Chamilly
C
Andersson
Rolf
R
Srinivas
Uppugunduri
U
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000494:pharmacology*; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D007476:Ionophores / Q000494:pharmacology; D008985:Monensin / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology
D000970:Antineoplastic Agents; D005938:Glucocorticoids; D007375:Interleukin-1; D016209:Interleukin-8; D007476:Ionophores; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D007371:Interferon-gamma; D008985:Monensin; D003513:Cycloheximide