SP-A as a cytokine: surfactant protein-A-regulated transcription of surfactant proteins and other genes.
Pulmonary surfactant is a mixture of phospholipids and surfactant-associated proteins made by alveolar type II cells that is necessary for normal lung function. Surfactant secretion and reuptake by type II cells are regulated in part by interaction of surfactant protein-A (SP-A) with a specific receptor (SPAR) on type 11 cells. Several chemicals and hormones affect both surfactant secretion and also surfactant gene expression, but consequences of SP-A-SPAR interaction beyond regulating surfactant secretion and reuptake are unknown. Accordingly, we studied the effects of SP-A on surfactant protein gene transcription, mRNA levels, and transcript stability. SP-A elicited new transcription of surfactant proteins SP-A, SP-B, and SP-C and SPAR and c-Jun but had no effect on beta-actin or c-fos transcription. Antibody against SP-A receptor blocked SP-A-induced transcription, confirming that these actions of SP-A were receptor-mediated. SP-A effects on overall transcript levels were more complex. However, SP-A, SP-B, and SP-C mRNA levels doubled in SP-A-treated cells compared to controls. SP-A is known to stabilize surfactant, control its secretion and reuptake by type II cells, and augment host antimicrobial defenses. These data indicate that SP-A also acts as an autocrine cytokine: it binds its receptor and specifically regulates transcription of surfactant proteins and other genes.
Korutla
L
L
Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Strayer
D S
DS
D000199:Actins / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D016762:Genes, fos; D016758:Genes, jun; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism*; D011510:Proteolipids / Q000235:genetics* / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic