Toluene diisocyanate (TDI) induces calcium elevation and interleukine-4 (IL-4) release - early responses upon TDI stimulation.

Occupational exposure to toluene diisocyanats (TDI) may cause asthma. In asthma patients, the allergic syndromes correlate cytokine production with the elevation in cytosolic calcium concentration [Ca(2+)](c) of lymphocytes in airway. We previously found TDI induces calcium signaling in neuronal cells. TDI mainly gets into human body via inhalation; therefore this study investigated the possibility of TDI inducing the changes in [Ca(2+)](c) in airway. We used human lung epithelial cell line H1355, human T-cell line Jurkat, and human neuroblastoma SH-SY5Y cells to present the kinds of cells existing in airway. The changes of [Ca(2+)](c) were measured by Fura-2 fluorescent dye. Results show that TDI induced an elevation in [Ca(2+)](c )in those cell lines and two primary isolated cells, bovine adrenal chromaffin cells and human white blood cells. Cytokine release and their gene expressions of Jurkat cells and human white blood cells were measured by ELISA and reverse transcription polymerase chain reaction. TDI acutely promoted the interleukine-4 (IL-4) release significantly in both Jurkat cells and human white blood cells. TDI-induced IL-4 release was suppressed in the presence of 1,2-bis- (O-aminophenoxy)ethane-N,N,N',N'- tetraacetic acid (BAPTA), an intracellular Ca(2+) chelator, in Jurkat cells. In the hand of gene expression, TDI induced an increase in the mRNA level of TNF-alpha and IL-4 in Jurkat cells. We conclude that the release of IL-4 were coupled with the elevation in [Ca(2+)](c) induced by TDI. Further studies are required to clarify the roles of TDI-induced IL-4 secretion in acute inflammation.