B. Veronesi et al., Neuropeptides and capsaicin stimulate the release of inflammatory cytokines in a human bronchial epithelial cell line, NEUROPEPTID, 33(6), 1999, pp. 447-456
The role of neuropeptides in initiating and modulating airway inflammation
was examined in a human bronchial epithelial cell line (i.e. BEAS-2B). At a
range of concentrations, exposure of BEAS-2B cells to Substance P (SP) or
calcitonin gene related protein resulted in immediate increases in intracel
lular calcium ([Ca2+](i)), the synthesis of the transcripts for the inflamm
atory cytokines, IL-6, IL-8 and TNF alpha after 2 h exposure, and the relea
se of their proteins after 6 h exposure. Addition of thiorphan (100 nM), an
inhibitor of neutral endopeptidase, enhanced the levels of SP-stimulated c
ytokine release. Stimulation of IL-6 by SP occurred in a conventional recep
tor-mediated manner as demonstrated by its differential release by fragment
s SP 4-11 and SP 1-4 and by the blockage of IL-6 release with the non-pepti
de, NK-I receptor antagonist, CP-99 994. In addition to the direct stimulat
ion of inflammatory cytokines, SP (0.5 mu M), in combination with TNF alpha
(25 units/ml), synergistically stimulated IL-6 release. BEAS-2B cells also
responded to the botanical irritant, capsaicin (10 mu M) with increases in
[Ca2+](i) and IL-8 cytokine release after 4 h exposure. The IL-8 release w
as dependent on the presence of extracellular calcium. Capsaicin-stimulated
increases of [Ca2+](i) and cytokine release could be reduced to control le
vels by pre-exposure to capsazepine, an antagonist of capsaicin (i.e. vanil
loid) receptor(s) or by deletion of extracellular calcium from the exposure
media. The present data indicate that the BEAS-2B human epithelial cell li
ne expresses neuropeptide and capsaicin-sensitive pathways, whose activatio
n results in immediate increases of [Ca2+](i) stimulation of inflammatory c
ytokine transcripts and the release of their cytokine proteins. (C) 1999 Ha
rcourt Publishers Ltd.