Involvement of p38 MAPK, JNK, p42/p44 ERK and NF-κB in IL-1β-induced chemokine release in human airway smooth muscle cells

Asthma is an inflammatory disease, in which eotaxin, MCP-1 and MCP-3 play a crucial rote. These chemokines have been shown to be expressed and produced by IL-1beta-stimulated human airway smooth muscle cells (HASMC) in culture. In the present study we were interested to unravel the IL-1beta-induced signal transduction leading to chemokine production. Using Western blot, we observed an activation of p38 MAPK, JNK kinase and p42/p44 ERK when HASMC were stimulated with IL-1beta. We also observed a significant decrease in the expression and the release of eotaxin, MCP-1 and MCP-3 in the presence of SB203580, an inhibitor of p38 MAPK (71+/-6%, P<0.05, n = 8 and 39+/-10% P<0.01, n = 10 respectively), curcumin, an inhibitor of JNK kinase (83+/-4.9% and 88+/-3.4% respectively, P<0.01, n = 4). U0126, an inhibitor of p42/p44 ERK, also produced a significant decrease in chemokine production (46.3+/-9%, P<0.01 n = 10 and 67.8+/-12%, P<0.01, n = 12). Pyrrolydine dithiocarbamate, an inhibitor of NF-kappaB was also able to reduce the eotaxin, MCP-1 and MCP-3 expression and production (50+/-13%, P<0.05, n = 10 and 23+/-7%, P<0.05, n = 12). We conclude that p38 MAPK, JNK kinase, ERK and NF-kappaB are involved in the IL-1beta-induced eotaxin, MCP-1, and MCP-3 expression and release in HASMC. (C) 2003 Elsevier Science Ltd. All rights reserved.