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Expression of pro-fibrotic cytokines by eosinophils in asthma: Role of Th-2 cytokines FREE TO VIEW

Ron Olivenstein, MD; Séverine Létuvé, PhD*; Philippe Joubert, MSc; Qutayba Hamid, MD, PhD
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McGill University, Montréal, PQ, Canada


Chest. 2004;126(4_MeetingAbstracts):758S-c-759S. doi:10.1378/chest.126.4_MeetingAbstracts.758S-c
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PURPOSE:  Eosinophils are suggested to play a role in airway remodeling in asthma. It was hypothesized that stimulation of eosinophils with Th2-type cytokines would induce the expression of the pro-fibrotic cytokines TGF-beta1, IL-11 and IL-17.

METHODS:  Eosinophils were purified from the blood of asthmatic and control subjects. Cells were stimulated for 3-12 hours with Th2 or Th1 cytokines. Expression of TGF-beta1, IL-11 and IL-17 was studied at the mRNA and protein levels by Real-Time PCR and Immunocytochemistry.

RESULTS:  Using immunocytochemistry, we showed that freshly purified eosinophils from all donors expressed TGF-beta1, IL-11 and IL-17. There were increased numbers of eosinophils expressing IL-11 in asthma compared to controls. No difference was observed in the percentage of cells expressing either IL-17 or TGF-beta1. The intensity of immunoreactivity for all pro-fibrotic cytokines was increased in eosinophils purified from asthmatic patients compared to controls. Using Real-Time PCR, mRNA for TGF-beta1 and IL-11, but not IL-17, were constitutively expressed by eosinophils from all donors. IL-11 mRNA level was increased in eosinophils from asthmatics compared to controls. No significant difference was observed between TGF-beta1 mRNA in the two groups. Stimulation of eosinophils with Th2 (IL-5, IL-4, IL-13, IL-9 or GM-CSF ) or Th1 (IL-2, IL-12 or IFN-gamma) cytokines did not influence mRNA levels for TGF-beta1, IL-11 and IL-17.

CONCLUSION:  Our results suggest that the expression of pro-fibrotic cytokines in eosinophils is increased in asthma. Expression of TGF-beta1, IL-11 and IL-17 was not regulated by Th2 cytokines at the mRNA level in peripheral blood eosinophils. The effects of Th2 cytokines on intracellular levels, as well as on the release, of these pro-fibrotic cytokines by eosinophils is currently under investigation.

CLINICAL IMPLICATIONS:  Our results confirm the ability of eosinophils to produce pro-fibrotic cytokines and support their potential role in airway remodeling. This study will lead to a better understanding of the role of eosinophils and Th2 cytokines in tissue remodeling in asthma in order to identify new targets for future therapies.

DISCLOSURE:  S. Létuvé, None.

Tuesday, October 26, 2004

12:30 PM- 2:00 PM




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