Induction of tumor necrosis factor-alpha (TNF-alpha) in response to lead (Pb) exposure has been implicated in its immunotoxicity. However, the molecular mechanism by which Pb upregulates the level of TNF-alpha is wagely known. An attempt was therefore made to elucidate the mechanistic aspect of TNF-alpha induction, mainly focusing transcriptional and post transcriptional regulation via mitogen activated protein kinases (MAPKs) activation. We observed that exposure of Pb to human monocytic THP-1 cells resulted in significant enhanced production of INF-alpha m-RNA and protein secretion. Moreover, the stability of TNF-alpha m-RNA was also increased as indicated by its half life. Notably, activation of ERK 1/2, p38 and JNK in Pb exposed THP-1 was also evident. Specific inhibitor of ERK1/2. PD 98059 caused significant inhibition in production and stability of TNF-alpha m-RNA. However, SB 203580 partially inhibited production and stability of TNF-alpha m-RNA. Interestingly, a combined exposure of these two inhibitors completely blocked modulation of TNF-alpha m-RNA. Data tends to suggest that expression and stability of TNF-alpha induction due to Pb exposure is mainly regulated through ERK. Briefly, these observations are useful in understanding some mechanistic aspects of proinflammatory and immunotoxicity of Pb, a globally acknowledged key environmental contaminant. (C) 2011 Elsevier B.V. All rights reserved.