Ragweed-induced expression of GATA-3, IL-4, and IL-5 by eosinophils in the lungs of allergic C57BL/6J mice.
Allergen-induced recruitment of T lymphocytes and eosinophils to the airways is associated with increased expression of the transcription factor GATA-3. In this study, the relationship between airway inflammation and GATA-3 expression in the lungs was investigated using ragweed-sensitized C57BL/6J mice. Intratracheal ragweed challenge increased both the number of GATA-3-expressing cells in the perivascular and peribronchial regions and the amount of expression per cell. Interleukin (IL)-4 and IL-5 levels in bronchoalveolar lavage fluid were upregulated in parallel with GATA-3 expression. GATA-3 mRNA and protein colocalized to eosinophils. Eosinophils isolated from the lungs and stimulated with phorbol 12-myristate 13-acetate and/or A-23187 released IL-5. The release was inhibited by actinomycin D, which indicates that de novo synthesis of the cytokine was involved. Western blot analysis of proteins from isolated eosinophils demonstrated expression of the p50 subunit of nuclear factor-kappaB, a transcription factor that is implicated in control of GATA-3 expression. These data provide evidence that allergen challenge increases GATA-3 and proinflammatory cytokine expression by pulmonary eosinophils, which could provide positive feedback for the inflammatory response.
Justice
J Paul
JP
Department of Physiology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858, USA.
Borchers
M T
MT
Lee
J J
JJ
Rowan
W H
WH
Shibata
Y
Y
Van Scott
M R
MR
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology; D001798:Blood Proteins / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D050990:GATA3 Transcription Factor; D015870:Gene Expression / Q000276:immunology; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000032:analysis* / Q000096:biosynthesis; D015848:Interleukin-5 / Q000032:analysis* / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010940:Plant Proteins / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D012260:Ribonucleases; D018418:Th2 Cells / Q000276:immunology; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics*; D014158:Transcription, Genetic / Q000276:immunology
D000485:Allergens; D001798:Blood Proteins; D004268:DNA-Binding Proteins; D047091:Eosinophil Granule Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D015848:Interleukin-5; D010940:Plant Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D015847:Interleukin-4; D012260:Ribonucleases