Exposure to
environmental pollutants has been linked to various airway diseases and disease exacerbations. Almost all chronic airway diseases such as
chronic obstructive pulmonary disease and
asthma are caused by complicated interactions between gene and environment. One of the major hallmarks of those diseases is airway mucus overproduction (MO). Excessive mucus causes
airway obstruction and significantly increases morbidity and mortality. Metals are major components of environmental particulate matters (PM). Among them,
vanadium has been suggested to play an important role in PM-induced
mucin production.
Vanadium pentoxide (V(2)O(5)) is the most common commercial source of
vanadium, and it has been associated with occupational
chronic bronchitis and
asthma, both of which are MO diseases. However, the underlying mechanism is not entirely clear. In this study, we used both in vitro and in vivo models to demonstrate the robust inductions of
mucin production by V(2)O(5). Furthermore, the follow-up mechanistic study revealed a novel v-raf-1 murine
leukemia viral oncogene homolog 1-IKK-NF-κB pathway that mediated V(2)O(5)-induced
mucin production. Most interestingly, the
reactive oxygen species and the classical
mucin-inducing
epidermal growth factor receptor (EGFR)-MAPK pathway appeared not to be involved in this process. Thus the V(2)O(5)-induced
mucin production may represent a novel EGFR-MAPK-independent and environmental toxicant-associated MO model. Complete elucidation of the signaling pathway in this model will not only facilitate the development of the treatment for V(2)O(5)-associated
occupational diseases but also advance our understanding on the EGFR-independent
mucin production in other chronic airway diseases.