BPIFB1 (LPLUNC1) is upregulated in cystic fibrosis lung disease

Bingle, Colin D.; Wilson, Kirsty; Musa, Maslinda; Araujo, Bianca; Rassl, Doris M.; Wallace, William; LeClair, Elizabeth E.; Mauad, Thaís; Zhou, Zhe; Mall, Marcus

doi:10.1007/s00418-012-0990-8

Cited by 31 publications

(37 citation statements)

References 44 publications

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“…It is important to note that BPIFB1 staining is restricted to the airway epithelium, suggesting that the precise spatial expression of the protein is maintained in severe disease. These data are also consistent with our previous reports of elevated staining of BPIFB1 in goblet cells in the airways of patients with cystic fibrosis (8) and IPF (2). Presence of the glycosylated form of BPIFB1 in sputum is in agreement with the suggested function of BPIFB1 in airway defense, since effective clearance of mucus requires a balance of sputum volume and viscoelasticity.…”

Section: Discussionsupporting

confidence: 92%

“…Finally, we showed that BPIFB1 is localized to regions of goblet cell metaplasia. In addition to our previous proteomic study of COPD patients (24), elevated levels of BPIFB1 have been discovered in proteomic screening for other respiratory diseases, such as in the lung tissue of patients with cystic fibrosis (8), in sputum from patients with severe uncontrolled asthma (18), and in BALF from asthma patients after segmental allergen challenge (39). It is likely that sputum BPIFB1 levels reflect the homeostasis of the respiratory epithelium and may be upregulated in COPD as a result of smoking, chronic infection, and enhanced immune responses.…”

Section: Discussionmentioning

confidence: 98%

“…BPIFB1 has previously been identified in the proteome of nasal mucous (11) and induced sputum (10,22,24), and elevated levels of the protein were detected in a proteomic study of BALF from asthmatic patients after segmental allergen challenge (39). BPIFB1 expression is increased in advanced cystic fibrosis (8) and it is also robustly expressed in the bronchiolized epithelium lining the honeycomb cysts in usual interstitial pneumonia (2). BPIFA1 is the best characterized member of the PLUNC family and previous studies have identified multiple protective roles against respiratory infections and inflammation (9).…”

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confidence: 98%

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Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary disease: a longitudinal study

Gao

Ohlmeier

Nieminen

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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-A previous study involving a proteomic screen of induced sputum from smokers and patients with chronic obstructive pulmonary disease (COPD) demonstrated elevated levels of bactericidal/permeability-increasing foldcontaining protein B1 (BPIFB1). The aim of the present study was to further evaluate the association of sputum BPIFB1 levels with smoking and longitudinal changes in lung function in smokers with COPD. Sputum BPIFB1 was characterized by two-dimensional gel electrophoresis and mass spectrometry. The expression of BPIFB1 in COPD was investigated by immunoblotting and immunohistochemistry using sputum and lung tissue samples. BPIFB1 levels were also assessed in induced sputum from nonsmokers (n ϭ 31), smokers (n ϭ 169), and patients with COPD (n ϭ 52) via an ELISA-based method. The longitudinal changes in lung function during the 4-year follow-up period were compared with the baseline sputum BPIFB1 levels. In lung tissue samples, BPIFB1 was localized to regions of goblet cell metaplasia. Secreted and glycosylated BPIFB1 was significantly elevated in the sputum of patients with COPD compared with that of smokers and nonsmokers. Sputum BPIFB1 levels correlated with pack-years and lung function as measured by forced expiratory volume in 1 s (FEV 1) % predicted and FEV1/FVC (forced vital capacity) at baseline and after the 4-year follow-up in all participants. The changes in lung function over 4 years were significantly associated with BPIFB1 levels in current smokers with COPD. In conclusion, higher sputum concentrations of BPIFB1 were associated with changes of lung function over time, especially in current smokers with COPD. BPIFB1 may be involved in the pathogenesis of smokingrelated lung diseases.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 98%

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confidence: 98%

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Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary disease: a longitudinal study

Gao

Ohlmeier

Nieminen

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Goblet cells do not produce SPLUNC1 (46). Other changes in the subsets of proximal, lower respiratory tract airway epithelial cells will likely affect SPLUNC1 production.…”

Section: Discussionmentioning

confidence: 99%

Short Palate, Lung, and Nasal Epithelial Clone–1 Is a Tightly Regulated Airway Sensor in Innate and Adaptive Immunity

Britto

Liu

Curran

et al. 2013

Am J Respir Cell Mol Biol

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Short palate, lung, and nasal epithelial clone-1 (SPLUNC1) is a protein abundantly expressed by the respiratory epithelium of the proximal lower respiratory tract, a site of great environmental exposure. Previous studies showed that SPLUNC1 exerts antimicrobial effects, regulates airway surface liquid and mucociliary clearance, and suppresses allergic airway inflammation. We studied SPLUNC1 to gain insights into its role in host defense. In the lower respiratory tract, concentrations of SPLUNC1 are high under basal conditions. In models of pneumonia caused by common respiratory pathogens, and in Th1-induced and Th2-induced airway inflammation, SPLUNC1 secretion is markedly reduced. Pathogen-associated molecular patterns and IFN-g act directly on airway epithelial cells to inhibit SPLUNC1 mRNA expression. Thus, SPLUNC1 is quickly suppressed during infection, in response to an insult on the epithelial surface. These experiments highlight the finely tuned fluctuations of SPLUNC1 in response to exposures in the respiratory tract, and suggest that the loss of SPLUNC1 is a crucial feature of host defense across airbreathing animal species.Keywords: SPLUNC1; inflammation; innate; immunity; mucosaThe respiratory tract continuously interacts with environmental irritants and pathogens. These stimuli constitute part of an intricate network of signals that activate host defenses. Airway epithelial cells participate actively in this process by producing antimicrobial and immune mediators that maintain homeostasis during steady-state conditions, and promote inflammation during injury.The palate, lung, and nasal epithelial clone (PLUNC) genes are members of the bactericidal permeability-increasing protein foldcontaining (BPIF)/PLUNC protein family (1, 2). These genes are focally expressed by epithelial cells throughout the respiratory tracts of multiple air-breathing vertebrates (3). In total, 11 human genes and 14 murine genes have been described to date, located within a single locus on chromosome 20 and chromosome 2, respectively (4, 5). These genes code for the PLUNC proteins, which are classified into six short and eight long PLUNCs, based on their lengths.Short PLUNC 1 (SPLUNC1) is a 25-kD protein secreted by epithelial cells in the upper airway and proximal lower respiratory tract (3, 6-10). SPLUNC1 is readily detected in human saliva and in nasal and bronchial epithelial washings at concentrations ranging from 34.7 ng/ml to 13.8 mg/ml (6, 10-12). In tracheal epithelial-cell supernatants SPLUNC1 constituted 10% of the total soluble protein, making it one of the most highly expressed proteins produced by airway epithelial cells (7).SPLUNC1 shares structural similarities with the immunomodulatory proteins bactericidal permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (4, 13-15). It was initially hypothesized to express antimicrobial functions, and has been shown to inhibit the growth of multiple pathogens (16-19), inhibit biofilm formation, and possess surfactant properties (20,21). Although mos...

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“…Thus, various studies have investigated the relationship of these proteins in the host defense system against aggressive agents. 25,26,27,28,29 Ciliated cells found in respiratory epithelium adjacent to palatal minor salivary glands demonstrated positive expression of BPIFA1. We also found early expression (from eight weeks) in epithelial cells lining the nasal cavity, nasal capsule, and laryngeal pharynx and in surface cells of the tongue.…”

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confidence: 99%

BPI-fold (BPIF) containing/plunc protein expression in human fetal major and minor salivary glands

Alves

Bingle

et al. 2017

Braz. oral res.

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The aim of this study was to determine expression, not previously described, of PLUNC (palate, lung, and nasal epithelium clone) (BPI-fold containing) proteins in major and minor salivary glands from very early fetal tissue to the end of the second trimester and thus gain further insight into the function of these proteins. Early fetal heads, and major and minor salivary glands were collected retrospectively and glands were classified according to morphodifferentiation stage. Expression of BPI-fold containing proteins was localized through immunohistochemistry. BPIFA2, the major BPI-fold containing protein in adult salivary glands, was detected only in the laryngeal pharynx; the lack of staining in salivary glands suggested salivary expression is either very late in development or is only in adult tissues. Early expression of BPIFA1 was seen in the trachea and nasal cavity with salivary gland expression only seen in late morphodifferentiation stages. BPIFB1 was seen in early neural tissue and at later stages in submandibular and sublingual glands. BPIFA1 is significantly expressed in early fetal oral tissue but BPIFB1 has extremely limited expression and the major salivary BPIF protein (BPIFA2) is not produced in fetal development. Further studies, with more sensitive techniques, will confirm the expression pattern and enable a better understanding of embryonic BPIF protein function.

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BPIFB1 (LPLUNC1) is upregulated in cystic fibrosis lung disease

Cited by 31 publications

References 44 publications

Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary disease: a longitudinal study

Elevated sputum BPIFB1 levels in smokers with chronic obstructive pulmonary disease: a longitudinal study

Short Palate, Lung, and Nasal Epithelial Clone–1 Is a Tightly Regulated Airway Sensor in Innate and Adaptive Immunity

BPI-fold (BPIF) containing/plunc protein expression in human fetal major and minor salivary glands

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