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Interleukin-1[beta] (IL-1[beta]) 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-[kappa]B (NF-[kappa]B) pathways for IL-1[beta]-induced vascular cell adhesion molecule (VCAM)-I expression were investigated in human tracheal smooth muscle cells (HTSMC). IL-1[beta] 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 N[H.sub.2]-terminal kinase (JNK; SP-600125). Consistently, IL-1[beta]-stimulated phosphorylation of p42/p44 MAPK, p38, and JNK was attenuated by pretreatment with U0126, SB-202190, or SP-600125, respectively. IL-1[beta]-induced VCAM- 1 expression was significantly blocked by the specific NF-[kappa]B inhibitors helenalin and pyrrolidine dithiocarbamate. As expected, IL-1[beta]-stimulated translocation of NF-[kappa]B into the nucleus and degradation of I[kappa]B-[alpha] 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-1[beta] exposure or by anti-VCAM-1 antibody. Together, these results suggest that in HTSMC, activation of p42/p44 MAPK, p38, JNK, and NF-[kappa]B pathways is essential for IL-1[beta]-induced VCAM-1 gene expression. These results provide new insight into the mechanisms of IL-1[beta] action that cytokines may promote inflammatory responses in airway disease. interleukin-1[beta]; mitogen-activated protein kinase; c-Jun N[H.sub.2]-terminal kinase; nuclear factor-[kappa]B; vascular cell adhesion molecule-1