title: Regulated gene expression in cultured type II cells of adult human lung.
abstract: Alveolar type II cells have multiple functions, including surfactant production and fluid clearance, which are critical for lung function. Differentiation of type II cells occurs in cultured fetal lung epithelial cells treated with dexamethasone plus cAMP and isobutylmethylxanthine (DCI) and involves increased expression of 388 genes. In this study, type II cells of human adult lung were isolated at approximately 95% purity, and gene expression was determined (Affymetrix) before and after culturing 5 days on collagen-coated dishes with or without DCI for the final 3 days. In freshly isolated cells, highly expressed genes included SFTPA/B/C, SCGB1A, IL8, CXCL2, and SFN in addition to ubiquitously expressed genes. Transcript abundance was correlated between fetal and adult cells (r = 0.88), with a subset of 187 genes primarily related to inflammation and immunity that were expressed >10-fold higher in adult cells. During control culture, expression increased for 8.1% of expressed genes and decreased for approximately 4% including 118 immune response and 10 surfactant-related genes. DCI treatment promoted lamellar body production and increased expression of approximately 3% of probed genes by > or =1.5-fold; 40% of these were also induced in fetal cells. Highly induced genes (> or =10-fold) included PGC, ZBTB16, DUOX1, PLUNC, CIT, and CRTAC1. Twenty-five induced genes, including six genes related to surfactant (SFTPA/B/C, PGC, CEBPD, and ADFP), also had decreased expression during control culture and thus are candidates for hormonal regulation in vivo. Our results further define the adult human type II cell molecular phenotype and demonstrate that a subset of genes remains hormone responsive in cultured adult cells.
authors.affiliation: Department of Pediatrics, University of California San Francisco, San Francisco, USA. ballardp@peds.ucsf.edu
authors.forename: Philip L
authors.initials: PL
authors.lastname: Ballard
authors.forename: Jae W
authors.initials: JW
authors.lastname: Lee
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Fang
authors.forename: Cheryl
authors.initials: C
authors.lastname: Chapin
authors.forename: Lennell
authors.initials: L
authors.lastname: Allen
authors.forename: Mark R
authors.initials: MR
authors.lastname: Segal
authors.forename: Horst
authors.initials: H
authors.lastname: Fischer
authors.forename: Beate
authors.initials: B
authors.lastname: Illek
authors.forename: Linda W
authors.initials: LW
authors.lastname: Gonzales
authors.forename: Venkatadri
authors.initials: V
authors.lastname: Kolla
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matthay
mesh_terms: D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000502:physiology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D051381:Rats
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D000242:Cyclic AMP
references.citation: Respir Res. 2001;2(1):33-46
references.pmid: 11686863
references.citation: Am J Physiol Lung Cell Mol Physiol. 2005 Jan;288(1):L179-89
references.pmid: 15447939
references.citation: Am J Physiol Lung Cell Mol Physiol. 2006 Feb;290(2):L242-9
references.pmid: 16143588
references.citation: J Mol Med (Berl). 2006 Apr;84(4):318-28
references.pmid: 16520944
references.citation: Inflamm Res. 2000 Dec;49(12):655-65
references.pmid: 11211915
references.citation: Lancet. 1999 Apr 24;353(9162):1412-3
references.pmid: 10227229
references.citation: Life Sci. 1997;60(23):2059-67
references.pmid: 9180360
references.citation: J Histochem Cytochem. 1999 Feb;47(2):129-37
references.pmid: 9889249
references.citation: J Physiol. 2006 May 1;572(Pt 3):625-38
references.pmid: 16497717
references.citation: J Huazhong Univ Sci Technolog Med Sci. 2007 Oct;27(5):498-500
references.pmid: 18060619
references.citation: Am J Physiol Lung Cell Mol Physiol. 2003 Sep;285(3):L569-77
references.pmid: 12754193
references.citation: Pediatr Pathol Mol Med. 2001 Sep-Oct;20(5):387-412
references.pmid: 11552739
references.citation: Endocrinology. 1987 Sep;121(3):1155-63
references.pmid: 2441978
references.citation: Am J Respir Crit Care Med. 2000 Jul;162(1):258-63
references.pmid: 10903251
references.citation: Bioinformatics. 2004 Jun 12;20(9):1464-5
references.pmid: 14962934
references.citation: Am J Respir Cell Mol Biol. 2007 Jun;36(6):661-8
references.pmid: 17255555
references.citation: Nature. 2008 Jul 24;454(7203):455-62
references.pmid: 18650916
references.citation: Biochim Biophys Acta. 1985 Jul 30;846(1):155-66
references.pmid: 3839418
references.citation: Cell. 2005 Jun 17;121(6):823-35
references.pmid: 15960971
references.citation: PLoS One. 2009;4(4):e5043
references.pmid: 19357784
references.citation: Am J Respir Cell Mol Biol. 2007 Feb;36(2):213-25
references.pmid: 16960125
references.citation: Lab Invest. 1975 Jun;32(6):736-45
references.pmid: 1171339
references.citation: Am J Respir Cell Mol Biol. 1998 Apr;18(4):554-61
references.pmid: 9533944
references.citation: Endocr Rev. 2007 Dec;28(7):707-25
references.pmid: 17916741
references.citation: J Biol Chem. 2005 May 13;280(19):18579-89
references.pmid: 15755725
references.citation: Am J Physiol. 1997 Aug;273(2 Pt 1):L347-54
references.pmid: 9277446
references.citation: Genes Dev. 1996 Jan 1;10(1):60-9
references.pmid: 8557195
references.citation: Biochem Biophys Res Commun. 1999 Sep 7;262(3):744-51
references.pmid: 10471396
references.citation: Genomics. 2006 Dec;88(6):675-681
references.pmid: 16949791
references.citation: Am J Respir Cell Mol Biol. 1995 Jan;12(1):50-5
references.pmid: 7811470
references.citation: Am J Physiol Lung Cell Mol Physiol. 2004 Feb;286(2):L382-7
references.pmid: 14578117
references.citation: J Appl Physiol (1985). 1986 May;60(5):1665-72
references.pmid: 3754860
references.citation: Cell Tissue Res. 2003 Jan;311(1):31-45
references.pmid: 12483282
references.citation: N Engl J Med. 2002 Dec 26;347(26):2141-8
references.pmid: 12501227
references.citation: Exp Lung Res. 2005 Jun;31(5):461-82
references.pmid: 16047415
references.citation: Antioxid Redox Signal. 2009 Oct;11(10):2453-65
references.pmid: 19358684
references.citation: Am J Respir Cell Mol Biol. 2006 Jul;35(1):65-71
references.pmid: 16498083
references.citation: Pediatr Res. 2007 Apr;61(4):404-9
references.pmid: 17515862
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Nov;283(5):L940-51
references.pmid: 12376347
references.citation: Am J Physiol. 1991 Feb;260(2 Pt 1):L161-7
references.pmid: 1996659
references.citation: Chin Med Sci J. 2000 Jun;15(2):93-7
references.pmid: 12901631
references.citation: Cancer Prev Res (Phila). 2008 Jul;1(2):112-8
references.pmid: 19138944
references.citation: Am J Respir Cell Mol Biol. 2004 Apr;30(4):500-9
references.pmid: 15033639
references.citation: Mol Cell Biol. 1994 Sep;14(9):5671-81
references.pmid: 8065304
references.citation: Am J Respir Cell Mol Biol. 1995 May;12(5):497-502
references.pmid: 7742013
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Jun;292(6):L1506-14
references.pmid: 17337509
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Feb;282(2):L267-76
references.pmid: 11792631
references.citation: Zhongguo Dang Dai Er Ke Za Zhi. 2007 Apr;9(2):155-8
references.pmid: 17448315
references.citation: Am J Respir Cell Mol Biol. 2006 Jun;34(6):727-37
references.pmid: 16474099
references.citation: Biochim Biophys Acta. 1988 Jun 30;970(2):146-56
references.pmid: 3382696
references.citation: Exp Mol Pathol. 1975 Feb;22(1):142-50
references.pmid: 163758
references.citation: J Lipid Res. 2006 Jun;47(6):1322-31
references.pmid: 16513897
references.citation: J Clin Endocrinol Metab. 1986 Apr;62(4):678-91
references.pmid: 3949950
references.citation: Endocr Rev. 1989 May;10(2):165-81
references.pmid: 2666118
references.citation: Am J Respir Cell Mol Biol. 1994 Aug;11(2):230-9
references.pmid: 8049084
references.citation: Biochim Biophys Acta. 1980 Jan 18;617(1):36-50
references.pmid: 6243488
references.citation: Stat Appl Genet Mol Biol. 2004;3:Article3
references.pmid: 16646809
references.citation: Pediatr Pulmonol. 1995 Oct;20(4):234-40
references.pmid: 8606853
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Nov;293(5):L1183-93
references.pmid: 17720875
references.citation: J Biol Chem. 2008 Apr 18;283(16):10330-8
references.pmid: 18256027
references.citation: J Biol Chem. 2007 Aug 17;282(33):24109-19
references.pmid: 17580309
references.citation: Cell Mol Biol (Noisy-le-grand). 1999 Mar;45(2):219-23
references.pmid: 10230731
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Jan;292(1):L249-57
references.pmid: 16997883
references.citation: Cell Res. 2009 Jan;19(1):71-88
references.pmid: 19002158
references.citation: Int J Cancer. 1994 Sep 1;58(5):629-37
references.pmid: 7521325