Phylogenetic and evolutionary analysis of the <i>PLUNC</i> gene family

Bingle, Colin D.

doi:10.1110/ps.03332704

Cited by 80 publications

(119 citation statements)

References 36 publications

(71 reference statements)

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“…Given the range of its antimicrobial functions and its retained structure in airbreathing vertebrates, BPIFA1 appears to have evolved to provide essential hostprotective functions (62). There is significant redundancy in antimicrobial effectors in animals; yet, BPIFA1 may be essential based on its location in the proximal airways and its high level under basal conditions.…”

Section: Biological Properties Of Bpifa1 Antimicrobialmentioning

confidence: 99%

Bactericidal/Permeability-Increasing Protein Fold–Containing Family Member A1 in Airway Host Protection and Respiratory Disease

Britto

Cohn

2015

Am J Respir Cell Mol Biol

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Section: Biological Properties Of Bpifa1 Antimicrobialmentioning

confidence: 99%

Bactericidal/Permeability-Increasing Protein Fold–Containing Family Member A1 in Airway Host Protection and Respiratory Disease

Britto

Cohn

2015

Am J Respir Cell Mol Biol

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“…SPLUNC1 shares structural similarities with the immunomodulatory proteins bactericidal permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (4,(13)(14)(15). It was initially hypothesized to express antimicrobial functions, and has been shown to inhibit the growth of multiple pathogens (16)(17)(18)(19), inhibit biofilm formation, and possess surfactant properties (20,21).…”

mentioning

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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“…The expression pattern of BPIFA2 (the human ortholog of rodent parotid secretory protein [PSP]) 59 is more restricted than that of other family members, as it is only found in the oral cavity. 19 Other PSP-related proteins, for example, bsp30, have been described in the saliva of cows and cattle and are highly expressed in parotid glands.…”

Section: ; 34 ; 52mentioning

confidence: 99%

Salivary BPIFA1 (SPLUNC1) and BPIFA2 (SPLUNC2 A) are modified by head and neck cancer radiotherapy

González‐Arriagada

Ramos

Silva

et al. 2015

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

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Objective: To determine the effects of radiotherapy on salivary BPIFA expression and to investigate the role of BPIFA in the development of known radiotherapy side effects. Materials and Methods:Unstimulated whole-mouth saliva was collected from 45 cancer patients (1 week before treatment, during the treatment, and 1 week after completion of radiotherapy) and from 20 controls. BPIFA1 and BPIFA2 expression was detected by western blotting and analyzed along with clinicopathologic data and side effects from the radiotherapy.Results: A facial radiation field was associated with lower salivary flow during and after radiotherapy and correlated with side effects, mainly mucositis. Salivary BPIFA1 expression levels were similar between the control group and the patient group before treatment. On the other hand, BPIFA2 levels were higher in the patient group before treatment compared with the control group. BPIFA concentration was modified by radiotherapy as BPIFA1 levels increased (P = .0081) and BPIFA2 decreased (P < .0001). Higher levels of BPIFA1 were associated with the presence of mucositis (P = .0363) and its severity (P = .0500). Conclusions:The present study found that levels of BPIFA1 and glycosylated forms of BPIFA2 are affected by radiotherapy, suggesting that these proteins may play a role in the oral microenvironment in irradiated patients with head and neck cancer. Statement of Clinical Relevance:The present study which showed that BPIFA proteins expression was modified in patients who underwent radiotherapy may contribute to better understanding the etiology and could be useful to improve the management of its side effects of radiotherapy.

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Phylogenetic and evolutionary analysis of the PLUNC gene family

Cited by 80 publications

References 36 publications

Bactericidal/Permeability-Increasing Protein Fold–Containing Family Member A1 in Airway Host Protection and Respiratory Disease

Bactericidal/Permeability-Increasing Protein Fold–Containing Family Member A1 in Airway Host Protection and Respiratory Disease

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

Salivary BPIFA1 (SPLUNC1) and BPIFA2 (SPLUNC2 A) are modified by head and neck cancer radiotherapy

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