Expression of IL-8 gene in human monocytes and lymphocytes: differential regulation by TNF and IL-1.
TNF-alpha and IL-1 were reported to be the most powerful inducers of IL-8 in a multitude of cells, including leukocytes. In this study, we investigated TNF-alpha- and IL-1-mediated regulation of IL-8 gene expression in non-fractionated PBMC, and purified monocyte (MO) and lymphocyte (LY) fractions. Our analysis revealed that purified human MO did not respond to exogenous TNF-alpha with the induction of IL-8 mRNA or protein, nor require endogenous TNF-alpha for IL-8 expression. In contrast, in the presence of exogenous IL-1alpha and IL-1beta a substantial enhancement of IL-8 mRNA and protein expression in MO was observed. Nevertheless, antibodies to IL-1alpha and IL-1beta were unable to downregulate the expression of IL-8 in resting adherent or Staphylococcus aureus Cowan 1 (SAC)-stimulated MO. In contrast with MO, purified LY and non-fractionated PBMC expressed IL-8 in response to exogenous TNF-alpha, similar to exogenous IL-1alpha and IL-1beta. As was seen with MO, antibodies to TNF-alpha, IL-1alpha and IL-1beta did not inhibit the expression of IL-8 in purified LY and non-fractionated PBMC stimulated with SAC and LPS. Taken together, our data demonstrate major differences in responsiveness of MO and LY to exogenous TNF-alpha and IL-1, and suggest relative autonomy of IL-8 gene expression in these cells that does not require accessory cytokines but can be induced directly by exogenous stimuli.
Chaly
Y V
YV
Foundation for Fundamental Researches of Republic of Belarus, Minsk, Belarus.
Selvan
R S
RS
Fegeding
K V
KV
Kolesnikova
T S
TS
Voitenok
N N
NN
D002448:Cell Adhesion; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D014176:Protein Biosynthesis / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D013211:Staphylococcus aureus / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha