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Eosinophil granule-derived major basic protein induces IL-8 expression in human intestinal myofibroblasts
G T Furuta1, S J Ackerman, J Varga
1Combined 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.
Clinical and Experimental Immunology
|September 30, 2000
Summary
Eosinophil major basic protein stimulates intestinal fibroblasts to produce IL-8, a key inflammatory mediator. This interaction may play a role in inflammatory diseases involving eosinophils.
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Eosinophil infiltration is common in allergic and inflammatory conditions.
- Eosinophil-derived mediators can exacerbate inflammatory responses.
Purpose of the Study:
- To investigate the effect of eosinophil granule proteins on intestinal myofibroblast IL-8 production.
- To explore the role of major basic protein (MBP) and eosinophil-derived neurotoxin (EDN) in initiating inflammatory signaling.
Main Methods:
- Intestinal myofibroblasts (18-Co cells) were treated with MBP, EDN, or poly-L-arginine (a synthetic MBP analogue).
- Interleukin-8 (IL-8) mRNA levels were assessed using Northern blot and RT-PCR.
- Quantification of immunoreactive IL-8 protein was performed via ELISA.
Main Results:
- MBP significantly induced IL-8 mRNA production and subsequent IL-8 protein release from myofibroblasts.
- EDN showed minimal stimulation of IL-8 release.
- Poly-L-arginine-induced IL-8 mRNA production was sensitive to actinomycin D, indicating de novo synthesis.
Conclusions:
- Eosinophils interact with intestinal fibroblasts, with MBP being a key mediator.
- This interaction promotes IL-8 production, potentially contributing to the pathogenesis of diseases characterized by tissue eosinophilia.
- Findings highlight a novel mechanism in eosinophil-driven inflammation within the gut.