FK506 (tacrolimus) inhibition of intracellular production and enhancement of interleukin 1alpha through glucocorticoid application to chemically treated human keratinocytes.
OBJECTIVE
Production of the proinflammatory cytokine interleukin (IL) 1alpha, which is stored in keratinocytes (KCs) and is multifunctional, may be enhanced by glucocorticoids. A study was made to confirm whether immunosuppressants such as the macrocyclic lactone FK506 (tacrolimus) possibly serve to modulate glucocorticoid- stimulated IL-1alpha production from chemically treated KCs.


METHODS
Using cultured human KCs, the effects of FK506 on the production of IL-1alpha treated with chemicals (trinitrobenzene sulfonic acid sodium salt, TNBS) plus hydrocortisone were analyzed by ELISA and mRNA expression of IL-1alpha using RT-PCR.


RESULTS
Intracellular IL-1alpha in TNBS-treated human KCs was increased with a low concentration of 10(-10)M of hydrocortisone. Further FK506 application inhibited significantly this increased production. The mRNA expression of IL-1alpha at various concentrations of chemicals was not remarkably different.


CONCLUSIONS
FK506may control the increase in IL-1alpha with glucocorticoid in KCs, suggesting FK506 to suppress harmful effects of glucocorticoids such as steroid rosacea.
Horiuchi
Y
Y
Department of Dermatology, Nagasaki University Graduate School of Medicine, Nagasaki, Japan. nu-yhori@jcom.home.ne.jp
Bae
S-J
SJ
Katayama
I
I
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology*; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D012333:RNA, Messenger; D014302:Trinitrobenzenesulfonic Acid; D006854:Hydrocortisone; D016559:Tacrolimus