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Combined stimulation with the T helper cell type 2 cytokines interleukin (IL)-4 and IL-10 induces mouse mast cell apoptosis.

Yeatman CF, Jacobs-Helber SM, Mirmonsef P, Gillespie SR, Bouton LA, Collins HA, Sawyer ST, Shelburne CP, Ryan JJ - J. Exp. Med. (2000)

Bottom Line: Mast cells are found in connective and mucosal tissues throughout the body.Apoptosis was coupled with decreased expression of bcl-x(L) and bcl-2.Additionally, we found that IgE cross-linkage or stimulation with stem cell factor enhanced the apoptotic abilities of IL-4 and IL-10.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Virginia Commonwealth University, Richmond, Virginia 23284, USA.

ABSTRACT
Mast cells are found in connective and mucosal tissues throughout the body. Their activation via immunoglobulin E (IgE)-antigen interactions is promoted by T helper cell type 2 (Th2) cytokines and leads to the sequelae of allergic disease. We now report a mechanism by which Th2 cytokines can regulate mast cell survival. Specifically, we find that interleukin (IL)-4 and IL-10 induce apoptosis in IL-3-dependent bone marrow-derived mast cells and peritoneal mast cells. This process required 6 d of costimulation with IL-3, IL-4, and IL-10, and expression of signal transducer and activator of transcription 6 (Stat6). Apoptosis was coupled with decreased expression of bcl-x(L) and bcl-2. While this process occurred independent of the Fas pathway, culture in IL-3+IL-4+IL-10 greatly sensitized mast cells to Fas-mediated death. Additionally, we found that IgE cross-linkage or stimulation with stem cell factor enhanced the apoptotic abilities of IL-4 and IL-10. Finally, IL-3-independent mastocytomas and mast cell lines were resistant to apoptosis induced by IL-3+IL-4+IL-10. These data offer evidence of Th2 cytokine-mediated homeostasis whereby these cytokines both elicit and limit allergic responses. Dysregulation of this pathway may play a role in allergic disease and mast cell tumor survival.

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Related in: MedlinePlus

IL-4 and IL-10 induce apoptosis in BMMCs cultured in IL-3 and SCF. Cells were stimulated for 6 d and assessed by PI staining. Resulting means and standard errors are from three experiments using four different BMMC populations. *P < 0.05.
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Figure 2: IL-4 and IL-10 induce apoptosis in BMMCs cultured in IL-3 and SCF. Cells were stimulated for 6 d and assessed by PI staining. Resulting means and standard errors are from three experiments using four different BMMC populations. *P < 0.05.

Mentions: Importantly, similar cultures containing IL-3 plus stem cell factor (SCF) consistently demonstrated equal or greater rates of proliferation than cultures receiving IL-3+IL-4+IL-10, yet demonstrated very low rates of apoptosis (Fig. 2, and data not shown). These data, coupled with the fact that our cultures were maintained at a low cell density and fed every 4 d, argue against exhaustion of medium components as an explanation for the observed apoptosis.


Combined stimulation with the T helper cell type 2 cytokines interleukin (IL)-4 and IL-10 induces mouse mast cell apoptosis.

Yeatman CF, Jacobs-Helber SM, Mirmonsef P, Gillespie SR, Bouton LA, Collins HA, Sawyer ST, Shelburne CP, Ryan JJ - J. Exp. Med. (2000)

IL-4 and IL-10 induce apoptosis in BMMCs cultured in IL-3 and SCF. Cells were stimulated for 6 d and assessed by PI staining. Resulting means and standard errors are from three experiments using four different BMMC populations. *P < 0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195863&req=5

Figure 2: IL-4 and IL-10 induce apoptosis in BMMCs cultured in IL-3 and SCF. Cells were stimulated for 6 d and assessed by PI staining. Resulting means and standard errors are from three experiments using four different BMMC populations. *P < 0.05.
Mentions: Importantly, similar cultures containing IL-3 plus stem cell factor (SCF) consistently demonstrated equal or greater rates of proliferation than cultures receiving IL-3+IL-4+IL-10, yet demonstrated very low rates of apoptosis (Fig. 2, and data not shown). These data, coupled with the fact that our cultures were maintained at a low cell density and fed every 4 d, argue against exhaustion of medium components as an explanation for the observed apoptosis.

Bottom Line: Mast cells are found in connective and mucosal tissues throughout the body.Apoptosis was coupled with decreased expression of bcl-x(L) and bcl-2.Additionally, we found that IgE cross-linkage or stimulation with stem cell factor enhanced the apoptotic abilities of IL-4 and IL-10.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Virginia Commonwealth University, Richmond, Virginia 23284, USA.

ABSTRACT
Mast cells are found in connective and mucosal tissues throughout the body. Their activation via immunoglobulin E (IgE)-antigen interactions is promoted by T helper cell type 2 (Th2) cytokines and leads to the sequelae of allergic disease. We now report a mechanism by which Th2 cytokines can regulate mast cell survival. Specifically, we find that interleukin (IL)-4 and IL-10 induce apoptosis in IL-3-dependent bone marrow-derived mast cells and peritoneal mast cells. This process required 6 d of costimulation with IL-3, IL-4, and IL-10, and expression of signal transducer and activator of transcription 6 (Stat6). Apoptosis was coupled with decreased expression of bcl-x(L) and bcl-2. While this process occurred independent of the Fas pathway, culture in IL-3+IL-4+IL-10 greatly sensitized mast cells to Fas-mediated death. Additionally, we found that IgE cross-linkage or stimulation with stem cell factor enhanced the apoptotic abilities of IL-4 and IL-10. Finally, IL-3-independent mastocytomas and mast cell lines were resistant to apoptosis induced by IL-3+IL-4+IL-10. These data offer evidence of Th2 cytokine-mediated homeostasis whereby these cytokines both elicit and limit allergic responses. Dysregulation of this pathway may play a role in allergic disease and mast cell tumor survival.

Show MeSH
Related in: MedlinePlus