Tissue distribution of the secretory protein, SPLUNC1, in the human fetus

Abstract

We previously identified a tissue-specific gene, short palate, lung, and nasal epithelium clone 1 (SPLUNC1), in nasopharyngeal epithelial tissues. SPLUNC1 was differentially expressed in nasopharyngeal carcinoma. Bioinformatic analysis revealed that SPLUNC1 has the bactericidal permeability-increasing protein/lipid-binding protein (BPI/LBP) domain and a 19 amino acid signal peptide, which suggest that it is a secretory protein. Its precise cellular localization in the respiratory tract is mainly in mucous cells and ducts of submucosal glands. However, little is known about its expression pattern in various human tissues. We generated a highly specific antibody and analyzed its distribution in the human fetus by immunohistochemistry to more precisely determine SPLUNC1 protein localization in human tissues. The results were further validated by RT-PCR. Our results showed that SPLUNC1 protein is expressed at not only the serous glands and epithelium of the upper respiratory tract and digestive tract, but also in the oculi of human embryos. Interestingly, we also found positive staining in fetus adipose tissue, a result not previously reported in studies of adult human tissues. Western blot analysis detected a 24 kDa SPLUNC1 protein in the compounds of nasopharyngeal secretions. This secretory protein was also detected in saliva and tears. Our research suggests that SPLUNC1 protein may not only be an antimicrobial peptide that plays an important role in the maintenance of homeostasis in the upper respiratory tract, oculi, and alimentary tract, it may also be important in the development and lipid metabolism of the adipose tissue.

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

“…The anatomical distribution of BPIFA1 protein expression in human fetuses is similar to that observed in adults (40). In upper respiratory tract secretions, BPIFA1 can be detected in saliva, nasal lavage fluid, and middle ear effusions (9,14,24,32,34,40,44). In lower respiratory tract secretions, BPIFA1 has been detected in sputum, tracheal secretions, airway lining fluid, and bronchoalveolar lavage fluid (BALF) (9,18,23).…”

“…BPIFA1 was also detected in the parotid gland and submucosal glands of nasal polyps, tongue, and sinus tissue but not on their surface epithelium (18,19,36,38). The anatomical distribution of BPIFA1 protein expression in human fetuses is similar to that observed in adults (40). In upper respiratory tract secretions, BPIFA1 can be detected in saliva, nasal lavage fluid, and middle ear effusions (9,14,24,32,34,40,44).…”

SPLUNC1 reduces the inflammatory response of nasopharyngeal carcinoma cells infected with the EB virus by inhibiting the TLR9/NF-κB pathway

“…The coding region of the SPLUNC1 gene was inserted into the pEGFP vector as previously described (14). The plasmid p2089 (Maxi-EBV), which contained the complete EBV genome of the B95-8 strain was kindly provided by Professor W. Hammerschmidt (GSF-National Research Center for Environment and Health, Germany).…”

SPLUNC1 Deficiency Enhances Airway Eosinophilic Inflammation in Mice

“…SPLUNC1 was predicted to exert host defense functions, based on its sequence homology with other known antimicrobial proteins such as bactericidal permeability increasing protein and LPS-binding protein (LBP) (9). We previously demonstrated that the Th2 cytokine IL-13 significantly reduces SPLUNC1 expression and secretion from well-differentiated human primary airway epithelial cells, rendering a host susceptible to bacterial infections (10).…”