A potent immunosuppressant FK506 inhibits IL-8 expression in human eosinophils.
FK506, a potent immunosuppressant, has attracted attention for its potential effectiveness in allergic diseases. Although eosinophils are believed to be one of the important effector cells at the site of allergic inflammation, there have been few reports about the direct effect of FK506 on eosinophils. In the present study, we evaluated if FK506 had any effect on the production of IL-8, one of the important chemokines for a variety of inflammatory cells, from human peripheral eosinophils. Purified eosinophils constitutively released IL-8, which was increased with calcium ionophore (10(-6) M). FK506 showed a dose-dependent suppressive effect on IL-8 production by eosinophils stimulated with calcium ionophore, but showed no effect on unstimulated cells. Evaluation of IL-8 mRNA levels by reverse transcription and polymerase chain reaction demonstrated that FK506 suppressed IL-8 gene expression only in activated eosinophils. FK506 further showed a suppressive effect on eotaxin and MCP-1 release from eosinophils. These findings suggested that FK506 might prevent infiltration of inflammatory cells such as eosinophils by, at least in part, inhibiting chemokine release from eosinophils.
D001483:Base Sequence; D054413:Chemokine CCL11; D018932:Chemokine CCL2 / Q000378:metabolism; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology* / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology*