TRPV4 is not the molecular sensor for bacterial lipopolysaccharides-induced calcium signaling.

Lipopolysaccharides (LPS) is one of the most potent pathogen-associated signals for the immune system of vertebrates. In addition to the canonical pathway of LPS detection mediated by toll-like receptor 4 (TLR4) signaling pathway, TRP channel-mediated pathways endow sensory neurons and epithelial cells with the ability to detect and react to bacterial endotoxins. Previous work revealed that LPS triggers TRPV4-dependent calcium influx in urothelial cells (UCs) and mouse tracheobronchial epithelial cells (mTEC). In marked contrast, here we show that most subtypes of LPS could not directly activate TRPV4 channel. Although LPS from Salmonella enterica serotype Minnesota evoked a [Ca] response in freshly isolated human bronchial epithelial cells (ECs), freshly isolated mouse ear skin single-cell suspensions, or HEK293T cells transiently transfected with mTRPV4, this activation occurred in a TRPV4-independent manner. Additionally, LPS from either E. coli strains or Salmonella enterica serotype Minnesota did not evoke significant difference in inflammation and pain hyperalgesia between wild type and TRPV4 deficient mice. In summary, our results demonstrate that in vitro and in vivo effects induced by LPS are independent of TRPV4, thus providing a clarity to the questioned role of LPS in TRPV4 activation.