Involvement of p42/p44 MAPK, JNK, and NF-κB in IL-1β-induced ICAM-1 expression in human pulmonary epithelial cells

✍ Scribed by Feng-Shu Lin; Chih-Chung Lin; Chin-Sung Chien; Shu-Feng Luo; Chuen-Mao Yang

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 393 KB
• Volume: 202
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.20142

✦ Synopsis

Abstract

Interleukin‐1β (IL‐1β) has been shown to induce the expression of intercellular adhesion molecule‐1 (ICAM‐1) on airway epithelial cells and contributes to inflammatory responses. However, the mechanisms regulating ICAM‐1 expression by IL‐1β in human A549 cells was not completely understood. Here, the roles of mitogen‐activated protein kinases (MAPKs) and NF‐κB pathways for IL‐1β‐induced ICAM‐1 expression were investigated in A549 cells. IL‐1β induced expression of ICAM‐1 protein and mRNA in a time‐ and concentration‐dependent manner. The IL‐1β induction of ICAM‐1 mRNA and protein were partially inhibited by U0126 and PD98059 (specific inhibitors of MEK1/2) and SP600125 [a specific inhibitor of c‐Jun‐N‐terminal kinase (JNK)]. U0126 was more potent than other inhibitors to attenuate IL‐1β‐induced ICAM‐1 expression. Consistently, IL‐1β stimulated phosphorylation of p42/p44 MAPK and JNK which was attenuated by pretreatment with U0126 or SP600125, respectively. Moreover, transfection with dominant negative mutants of MEK1/2 (MEK K97R) or ERK2 (ERK2 K52R) also attenuated IL‐1β‐induced ICAM‐1 expression. The combination of PD98059 and SP600125 displayed an additive effect on IL‐1β‐induced ICAM‐1 gene expression. IL‐1β‐induced ICAM‐1 expression was almost completely blocked by a specific NF‐κB inhibitor helenalin. Consistently, IL‐1β stimulated translocation of NF‐κB into the nucleus and degradation of IκB‐α which was blocked by helenalin, U0126, or SP600125. Taken together, these results suggest that activation of p42/p44 MAPK and JNK cascades, at least in part, mediated through NF‐κB pathway is essential for IL‐1β‐induced ICAM‐1 gene expression in A549 cells. These results provide new insight into the mechanisms of IL‐1β action that cytokines may promote inflammatory responses in the airway disease. © 2004 Wiley‐Liss, Inc.