Induction of IL-8 expression in T cells uses the CD28 costimulatory pathway.
IL-8, a potent chemotactic factor for neutrophil granulocytes and lymphocytes, is a proinflammatory cytokine secreted by a variety of cell types, including T cells. Stimulation of the CD28 cell surface molecule delivers costimulatory signals essential for lymphokine production in activated T cells via a conserved sequence element found in the promoter of several lymphokine genes. Anti-CD28-stimulated T cells produced significant amounts of IL-8; additionally, costimulation with anti-CD3 and anti-CD28 Abs resulted in a synergistic induction of IL-8 secretion. Sequence homology, single nucleotide mutations, and anti-CD28 Ab stimulation studies established that the NF-kappa B-like sequence in the promoter of the IL-8 gene functioned as a CD28 response element. Furthermore, cyclosporin A, but not rapamycin, blocked the synergistic induction of IL-8 expression achieved with anti-CD3 and anti-CD28 costimulation. The involvement of a CD28 response element in the induction of IL-8 expression in activated T cells may provide new insights into the pathogenesis and persistence of immune disorders characterized by increased levels of IL-8, such as psoriasis and rheumatoid arthritis.
Wechsler
A S
AS
Department of Medicine, Beth Israel Hospital, Boston, MA 02215.
Gordon
M C
MC
Dendorfer
U
U
LeClair
K P
KP
D001483:Base Sequence; D018106:CD28 Antigens / Q000276:immunology*; D002460:Cell Line; D004586:Electrophoresis / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008156:Luciferases / Q000235:genetics; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection / Q000379:methods
D018106:CD28 Antigens; D016209:Interleukin-8; D016328:NF-kappa B; D014157:Transcription Factors; D008156:Luciferases