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2013 ; 304
(11
): G949-57
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Emerging neuropeptide targets in inflammation: NPY and VIP
#MMPMID23538492
Chandrasekharan B
; Nezami BG
; Srinivasan S
Am J Physiol Gastrointest Liver Physiol
2013[Jun]; 304
(11
): G949-57
PMID23538492
show ga
The enteric nervous system (ENS), referred to as the "second brain," comprises a
vast number of neurons that form an elegant network throughout the
gastrointestinal tract. Neuropeptides produced by the ENS play a crucial role in
the regulation of inflammatory processes via cross talk with the enteric immune
system. In addition, neuropeptides have paracrine effects on epithelial
secretion, thus regulating epithelial barrier functions and thereby
susceptibility to inflammation. Ultimately the inflammatory response damages the
enteric neurons themselves, resulting in deregulations in circuitry and gut
motility. In this review, we have emphasized the concept of neurogenic
inflammation and the interaction between the enteric immune system and enteric
nervous system, focusing on neuropeptide Y (NPY) and vasoactive intestinal
peptide (VIP). The alterations in the expression of NPY and VIP in inflammation
and their significant roles in immunomodulation are discussed. We highlight the
mechanism of action of these neuropeptides on immune cells, focusing on the key
receptors as well as the intracellular signaling pathways that are activated to
regulate the release of cytokines. In addition, we also examine the direct and
indirect mechanisms of neuropeptide regulation of epithelial tight junctions and
permeability, which are a crucial determinant of susceptibility to inflammation.
Finally, we also discuss the potential of emerging neuropeptide-based therapies
that utilize peptide agonists, antagonists, siRNA, oligonucleotides, and
lentiviral vectors.