PMID- 11034599
OWN - NLM
STAT- MEDLINE
DCOM- 20001109
LR  - 20190508
IS  - 0022-1007 (Print)
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Linking)
VI  - 192
IP  - 8
DP  - 2000 Oct 16
TI  - Combined stimulation with the T helper cell type 2 cytokines interleukin (IL)-4 
      and IL-10 induces mouse mast cell apoptosis.
PG  - 1093-103
AB  - 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.
FAU - Yeatman, C F 2nd
AU  - Yeatman CF 2nd
AD  - Department of Biology, Virginia Commonwealth University, Richmond, Virginia 
      23284, USA.
FAU - Jacobs-Helber, S M
AU  - Jacobs-Helber SM
FAU - Mirmonsef, P
AU  - Mirmonsef P
FAU - Gillespie, S R
AU  - Gillespie SR
FAU - Bouton, L A
AU  - Bouton LA
FAU - Collins, H A
AU  - Collins HA
FAU - Sawyer, S T
AU  - Sawyer ST
FAU - Shelburne, C P
AU  - Shelburne CP
FAU - Ryan, J J
AU  - Ryan JJ
LA  - eng
GR  - 1R01-AI43433/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Annexin A5)
RN  - 0 (Interleukin-3)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Stem Cell Factor)
RN  - 130068-27-8 (Interleukin-10)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Animals
MH  - Annexin A5/analysis
MH  - Apoptosis/*drug effects/immunology
MH  - Bone Marrow Cells/*cytology
MH  - Cells, Cultured
MH  - Flow Cytometry
MH  - Interleukin-10/*pharmacology
MH  - Interleukin-3/pharmacology
MH  - Interleukin-4/*pharmacology
MH  - Kinetics
MH  - Mast Cells/cytology/drug effects/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred Strains
MH  - Recombinant Proteins/pharmacology
MH  - Stem Cell Factor/pharmacology
MH  - Th2 Cells/*immunology
PMC - PMC2195863
EDAT- 2000/10/18 11:00
MHDA- 2001/02/28 10:01
PMCR- 2001/04/16
CRDT- 2000/10/18 11:00
PHST- 2000/10/18 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/18 11:00 [entrez]
PHST- 2001/04/16 00:00 [pmc-release]
AID - 990961 [pii]
AID - 10.1084/jem.192.8.1093 [doi]
PST - ppublish
SO  - J Exp Med. 2000 Oct 16;192(8):1093-103. doi: 10.1084/jem.192.8.1093.