Transcriptional stimulation of the surfactant protein B gene by STAT3 in respiratory epithelial cells.
The function of the lung is dependent upon differentiation and proliferation of respiratory epithelial cells and the synthesis/secretion of surfactant lipids and proteins into air space. During the respiratory inflammatory response, cytokines produced by macrophages and epithelial cells in the respiratory system have significant influence on surfactant protein homeostasis. We report here that among family members of Janus family tyrosine kinase (JAK) and signal transducers and activators of transcription (STAT), only JAK 1 and STAT3 stimulated the -500 to +41 promoter activity of the surfactant protein B (SP-B) gene in respiratory epithelial cells. JAK1 and STAT3 were co-localized in alveolar type II epithelial cells where SP-B is synthesized and secreted. Interleukin 6 and interleukin 11, known to activate STAT3 synergistically, stimulated the SP-B promoter activity with retinoic acid, which is at least partially mediated through interactions between STAT3 and retinoid nuclear receptor enhanceosome proteins in pulmonary epithelial cells.
Yan
Cong
C
Division of Pulmonary Biology, The Graduate Program for Molecular and Developmental Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. Cong.Yan@chmcc.org
Naltner
Angela
A
Martin
Michelle
M
Naltner
Michael
M
Fangman
Jessica M
JM
Gurel
Okyanus
O
D001059:Apoproteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D053613:Janus Kinase 1; D008156:Luciferases / Q000235:genetics; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D001059:Apoproteins; D004268:DNA-Binding Proteins; D017370:Interleukin-11; D015850:Interleukin-6; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C000607071:RARA protein, human; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; C046616:pulmonary surfactant apoprotein; D014212:Tretinoin; D008156:Luciferases; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1