IL-5 and granulocyte-macrophage colony-stimulating factor activate STAT3 and STAT5 and promote Pim-1 and cyclin D3 protein expression in human eosinophils.
Allergic inflammation is characterized by elevated eosinophil numbers and by the increased production of the cytokines IL-5 and GM-CSF, which control several eosinophil functions, including the suppression of apoptosis. The JAK/STAT pathway is important for several functions in hemopoietic cells, including the suppression of apoptosis. We report in this study that STAT3, STAT5a, and STAT5b are expressed in human eosinophils and that their signaling pathways are active following IL-5 or GM-CSF treatment. However, in airway eosinophils, the phosphorylation of STAT5 by IL-5 is reduced, an event that may be related to the reduced expression of the IL-5Ralpha on airway eosinophils. Furthermore, IL-5 and GM-CSF induced the protein expression of cyclin D3 and the kinase Pim-1, both of which are regulated by STAT-dependent processes in some cell systems. Pim-1 is more abundantly expressed in airway eosinophils than in blood eosinophils. Because Pim-1 reportedly has a role in the modulation of apoptosis, these results suggest that Pim-1 action is linked to the suppression of eosinophil apoptosis by these cytokines. Although cyclin D3 is known to be critical for cell cycle progression, eosinophils are terminally differentiated cells that do not proceed through the cell cycle. Thus, this apparent cytokine regulation of cyclin D3 suggests that there is an alternative role(s) for cyclin D3 in eosinophil biology.
Stout
Barbara A
BA
Department of Biomolecular Chemistry, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA.
Bates
Mary Ellen
ME
Liu
Lin Ying
LY
Farrington
Natasha N
NN
Bertics
Paul J
PJ
D000293:Adolescent; D000328:Adult; D002470:Cell Survival / Q000502:physiology; D056743:Cyclin D3; D016213:Cyclins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D004804:Eosinophils / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000502:physiology*; D006801:Humans; D015848:Interleukin-5 / Q000097:blood / Q000502:physiology*; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008894:Milk Proteins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D051573:Proto-Oncogene Proteins c-pim-1; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D014443:Tyrosine / Q000378:metabolism
C534696:CCND3 protein, human; D056743:Cyclin D3; D016213:Cyclins; D004268:DNA-Binding Proteins; D015848:Interleukin-5; D008894:Milk Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D014443:Tyrosine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C496634:PIM1 protein, human; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1