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

Abstract

Asthma is an inflammatory disease, in which eotaxin, MCP-1 and MCP-3 play a crucial role. These chemokines have been shown to be expressed and produced by IL-1β-stimulated human airway smooth muscle cells (HASMC) in culture. In the present study we were interested to unravel the IL-1β-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-1β. 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-κB 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-κB are involved in the IL-1β-induced eotaxin, MCP-1, and MCP-3 expression and release in HASMC.