The Role of BPIFA1 in Upper Airway Microbial Infections and Correlated Diseases

Abstract

The mucosa is part of the first line of immune defense against pathogen exposure in humans and prevents viral and bacterial infection of the soft palate, lungs, uvula, and nasal cavity that comprise the ear-nose-throat (ENT) region. Bactericidal/permeability-increasing fold containing family A, member 1 (BPIFA1) is a secretory protein found in human upper aerodigestive tract mucosa. This innate material is secreted in mucosal fluid or found in submucosal tissue in the human soft palate, lung, uvula, and nasal cavity. BPIFA1 is a critical component of the innate immune response that prevents upper airway diseases. This review will provide a brief introduction of the roles of BPIFA1 in the upper airway (with a focus on the nasal cavity, sinus, and middle ear), specifically its history, identification, distribution in various human tissues, function, and diagnostic value in various upper airway infectious diseases.

Figure 1

The genomic location of BPIFA1 and related BPI family members. BPIFA1 is located on chromosome 20q11.2 and contains nine exons. There are 7 BPIF gene families located in loci of BPIFA1, BPIFA2, BPIFA3, BPIFB1, BPIFB2, BPIFB3, and BPIFB4.

Figure 2

Highly specific expression of BPIFA1 in the human upper airway respiratory system. The major expressed tissues of BPIFA1 are located in the tongue, tonsil, nasal polyps, adenoid, and middle ear (as shown in the left panel). Those lowering BPIFA1 expression are affected by infections and correlated diseases of upper airway tracts (as shown in the right panel).

Figure 3

Proposed mechanism of IL-13 inhibition of LPS-induced BPIFA1 expression in nasal polyps and adenoid tissue. The IL-13 inhibits BPIFA1 (SPLUNC1) gene expression through a JNK/c-Jun regulation pathway. Lactoferrin also interacts with BPIFA1 in the nasal polyps and adenoid tissues to avoid LPS-induced inflammation via downregulated MEK1/2-MAPK signaling.