In:
American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 288, No. 2 ( 2005-02), p. L227-L237
Abstract:
Interleukin-1β (IL-1β) has been shown to induce the expression of adhesion molecules on airway epithelial and smooth cells and contributes to inflammatory responses. Here, the roles of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) pathways for IL-1β-induced vascular cell adhesion molecule (VCAM)-1 expression were investigated in human tracheal smooth muscle cells (HTSMC). IL-1β induced expression of VCAM-1 protein and mRNA in a time-dependent manner, which was significantly inhibited by inhibitors of MEK1/2 (U0126 and PD-98059), p38 (SB-202190), and c-Jun NH 2 -terminal kinase (JNK; SP-600125). Consistently, IL-1β-stimulated phosphorylation of p42/p44 MAPK, p38, and JNK was attenuated by pretreatment with U0126, SB-202190, or SP-600125, respectively. IL-1β-induced VCAM-1 expression was significantly blocked by the specific NF-κB inhibitors helenalin and pyrrolidine dithiocarbamate. As expected, IL-1β-stimulated translocation of NF-κB into the nucleus and degradation of IκB-α were blocked by helenalin but not by U0126, SB-202190, or SP-600125. Moreover, the resultant enhancement of VCAM-1 expression increased the adhesion of polymorphonuclear cells to a monolayer of HTSMC, which was blocked by pretreatment with helenalin, U0126, SB-202190, or SP-600125 before IL-1β exposure or by anti-VCAM-1 antibody. Together, these results suggest that in HTSMC, activation of p42/p44 MAPK, p38, JNK, and NF-κB pathways is essential for IL-1β-induced VCAM-1 gene expression. These results provide new insight into the mechanisms of IL-1β action that cytokines may promote inflammatory responses in airway disease.
Type of Medium:
Online Resource
ISSN:
1040-0605
,
1522-1504
DOI:
10.1152/ajplung.00224.2004
Language:
English
Publisher:
American Physiological Society
Publication Date:
2005
detail.hit.zdb_id:
1477300-4
SSG:
12
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