Disease relevance of SFTPB

• The population frequency of five known and four novel SNPs was studied, providing as many potential markers for pulmonary disease related to SFTPB [1].
• To determine the molecular defect accounting for the deficiency of pulmonary surfactant protein B (SP-B) in full-term neonates who died from respiratory failure associated with alveolar proteinosis, the sequence of the SP-B transcript in affected infants was ascertained [2].
• Mutations in the gene encoding SP-B result in severe, fatal neonatal lung disease, and mutations in the gene encoding SP-C are associated with chronic interstitial lung diseases in newborns, older children, and adults [3].
• In contrast, staining for SP-A and SP-B is of limited value, because there is an unacceptably high rate of cross-reactivity between breast carcinomas metastatic to the lung and primary pulmonary carcinomas [4].
• In contrast, both SPA and SPB were positive in only 45% of pulmonary adenocarcinomas and in 10% and in 5% of the large cell carcinomas, respectively [5].

High impact information on SFTPB

• Elucidation of the structure and function of the hydrophobic surfactant protein (SP-B) and the SP-B gene has provided critical insight into surfactant homeostasis and control of respiratory epithelial cell gene expression [6].
• Analysis of the genetic controls governing the SP-B gene has led to the definition of DNA-protein interactions that determine respiratory epithelial cell gene expression in general [6].
• After secretion, SP-B plays an essential role in determining the structure of tubular myelin, the stability and rapidity of spreading, and the recycling of surfactant phospholipids [6].
• Thus, a complex including Bqt1 and Bqt2 is essential for connecting telomeres to the SPB [7].
• This genome-wide search identified two proteins, Bqt1 and Bqt2, that connect telomeres to the spindle-pole body (SPB; the centrosome equivalent in fungi) [7].

Chemical compound and disease context of SFTPB

• A single-nucleotide polymorphism (SNP) at nucleotide 1580 (C/T) in exon 4 of SP-B that changes amino acid 131 from threonine to isoleucine (Thr131-->Ile) is associated with several pulmonary diseases [8].
• A transgenic mouse in which human SP-B expression was placed under conditional control of doxycycline via the CCSP promoter was utilized to determine the role of SP-B in the initiation of pulmonary inflammation [9].
• We characterized the effects of cortisol and all trans-retinoic acid (RA) on SP-A and SP-B gene expression in H441 cells, a human pulmonary adenocarcinoma cell line [10].
• The use of genetically detoxified Bordetella pertussis adenylate cyclase toxin (CyaA) as a delivery system for two immunodominant proteins of M. tuberculosis that are of greater specificity than PPD, early-secreted antigenic target 6-kDa protein (ESAT-6) and culture filtrate protein 10 (CFP-10), was therefore investigated [11].
• Mycobacterium africanum Elicits an Attenuated T Cell Response to Early Secreted Antigenic Target, 6 kDa, in Patients with Tuberculosis and Their Household Contacts [12].

Biological context of SFTPB

• Taken together, these data are consistent with the view that an indel mutation occurred on a relatively common SFTPB haplotype and now accounts for the majority of (and possibly all) extant 121ins2 chromosomes [13].
• A frameshift mutation consisting of a substitution of GAA for C in codon 121 of the SP-B cDNA was identified [2].
• Deletion and site-specific mutagenesis analysis identified clustered retinoic acid-responsive element sites in the 5'-flanking enhancer region of the hSP-B gene that bound RARalpha proteins [14].
• Surfactant protein B (SP-B) is essential to the function of pulmonary surfactant and to alveolar type 2 cell phenotype [15].
• Previously, a promoter region of human SP-B gene from -64 to -118 has been identified as critical for the tissue-specific expression of this gene [16].

Anatomical context of SFTPB

• Immunohistochemical analysis detected CITED1 and SFTPB in 49/52 and 39/52 PTCs, respectively, but not in follicular thyroid carcinoma and normal thyroid tissue [17].
• Expression of SP-B by respiratory epithelial cells is regulated by developmental and hormonal influences at the level of gene transcription [14].
• Fluorescence immunocytochemistry using epitope-specific antisera showed colocalization of pro-SP-B with the endoplasmic reticulum resident protein BiP [15].
• To determine whether the C allele SP-B variant is indeed glycosylated at Asn(129)-Gln-Thr131, we first generated stably transfected Chinese hamster ovary cell lines that expressed each version of SP-B, and developed specific SP-B polyclonal anti-peptide antibodies [8].
• Surfactant protein B (SP-B) is a hydrophobic, 79 amino acid peptide that regulates the structure and function of surfactant phospholipid membranes in the airspaces of the lung [18].

Associations of SFTPB with chemical compounds

• 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 [19].
• In pulse-chase studies, brefeldin A blocked all processing of 42-kDa pro-SP-B whereas similar studies using monensin blocked the final N-terminal processing event of 9 to 8 kDa SP-B [15].
• TRH alone also increases TTF-1 and SP-B mRNA levels but to a lesser extent than Dex [20].
• In addition, we also confirmed that both SP-B variants contain another N-linked glycosylation site, Asn311-Ser-Ser313 [8].
• The N-terminal half of SP-B (residues 1-37), which includes the nonhelical N-terminal amino acids in addition to helices 1 and 2, promoted rapid liposome fusion whereas shorter peptides were significantly less effective [18].

Physical interactions of SFTPB

• We also determined whether specific SP-B variants interact with RDS susceptibility or protective SP-A variants to enhance or reduce risk for RDS [21].
• Elsewhere, a 6 kDa peptide covering the peptide chain from residues 4 to 52 was isolated and its inhibitory effect on the binding of lactotransferrin to both human PHA-activated lymphocytes and non-activated platelets was demonstrated [22].

Enzymatic interactions of SFTPB

• Furthermore, addition of control SP-B can improve samples containing oxidized SP-C, but not vice versa [23].

Co-localisations of SFTPB

• JAK1 and STAT3 were co-localized in alveolar type II epithelial cells where SP-B is synthesized and secreted [19].

Regulatory relationships of SFTPB

• In vivo cotransfection studies further indicated that BR22 could act with TTF-1 to synergistically activate the SP-B promoter in mammalian cells [16].
• Overexpression of CREB, ATF-2 and c-Jun inhibited SP-B promoter activity in NCI-H441 cells [24].
• ABCA3 was coexpressed with SP-B and proSP-C in type II epithelial cells [25].
• To test the role of this bridge in SP-B function in vivo, a construct was generated in which cysteine residues 235 and 246 of the human SP-B proprotein were mutated to serine and cloned under the control of the 3.7-kilobase hSP-C promoter (hSP-B(C235S/C246S)) [26].
• Stepwise logistic regression analysis, duplex PCR data evaluation with recursive partition machine algorithm and hierarchical cluster analysis identified SFTPB (upregulated) and TFF3 (downregulated) gene combination as most favorable for differential molecular diagnosis of PTC [27].
• Using a well described model of type 2 cell differentiation, small interfering RNA knockdown of pepsinogen C inhibited production of mature SP-B, whereas overexpression of pepsinogen C increased SP-B production [28].

Other interactions of SFTPB

• Importantly, RA stimulation of the hSP-B promoter depends on tissue-specific thyroid transcription factor (TTF-1) DNA-binding sites [14].
• Markers in LTBP4 (p </= 0.05) and SFTPB (p = 0.005) were associated with 6-min walk test distance [29].
• RESULTS: At baseline, high levels of anti-GM-CSF antibodies and increased SP-A and SP-B levels were seen in all patients, and LDH was raised in 83% [30].
• No cDNA segment of SP-B, SP-C, or SP-D cDNA was amplified from isolated submucosal glands or superficial epithelial cells, whereas all were amplified from alveolar tissue [31].
• RESULTS: Nitrofen severely decreased TTF-1, HNF-3beta and SP-B mRNA expression by H441 pneumocytes in culture [32].

Analytical, diagnostic and therapeutic context of SFTPB

• Immunoprecipitation of the 42-kDa primary translation product is inhibited by the presence of the bovine 6-kDa protein [33].
• Chromatin immunoprecipitation assay demonstrated that retinoic acid treatment of H441 cells greatly stimulated both RAR and TTF-1 DNA binding to the hSP-B enhancer region in H441 cells [34].
• Human hydrophobic surfactant polypeptide, SP-B, purified from lung tissue by exclusion chromatography in organic solvents, has been characterized [35].
• PCR and direct sequence analysis of the SP-B gene revealed three novel mutations [36].
• We have mapped the human SP-B gene (SFTP3) to chromosome 2, band 2p12-->p11.2 by fluorescent in situ hybridization [37].

References