Eosinophil granule-derived major basic protein induces IL-8 expression in human intestinal myofibroblasts.
Eosinophil infiltration occurs in a variety of allergic and inflammatory diseases. The release of preformed mediators from eosinophils may contribute to inflammatory responses. We investigated the ability of eosinophil-derived major basic protein and eosinophil-derived neurotoxin to stimulate production of IL-8 from intestinal myofibroblasts. Intestinal myofibroblasts (18-Co cells) were incubated with major basic protein, eosinophil-derived neurotoxin, or a synthetic analogue of major basic protein, poly-L-arginine. Immunoreactive IL-8 was measured by ELISA and IL-8 mRNA levels were analysed by Northern blot or reverse transcription-polymerase chain assay. Major basic protein induced IL-8 mRNA production and release of significant levels of IL-8 immunoreactive protein. By contrast, eosinophil-derived neurotoxin stimulated little IL-8 release. The induction of IL-8 mRNA by poly-L-arginine was significantly inhibited by actinomycin D. These findings demonstrate a novel interaction between eosinophils and intestinal fibroblasts that may be involved in the pathogenesis of diseases associated with tissue eosinophilia.
Furuta
G T
GT
Combined Program in Pediatric Gastroenterology and Nutrition, The Children's Hospital and Massachusetts General Hospital, and the Division of Experimental Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
Ackerman
S J
SJ
Varga
J
J
Spiess
A M
AM
Wang
M Y
MY
Wershil
B K
BK
D001798:Blood Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D047091:Eosinophil Granule Proteins; D047208:Eosinophil-Derived Neurotoxin; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D007422:Intestines / Q000166:cytology; D009130:Muscle, Smooth / Q000166:cytology; D010455:Peptides / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012260:Ribonucleases; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D016209:Interleukin-8; D010455:Peptides; D011506:Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C015462:polyarginine; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases