Superfund Research Program
Assessing the Adverse Effects of Environmental Hazards on Reproductive Health
Project Leader: Bill L. Lasley
Grant Number: P42ES004699
Funding Period: 1995-2015
Project-Specific Links
Final Progress Reports
PublicationsConnect with the Grant Recipients
Final Progress Reports
Previous studies with triclocarban (TCC) indicated that the amplification effect required the presence of both an effective level of the sex steroid and its cognant nuclear receptor. Based on this information we posited that the action of glucocorticoids to suppress inflammation would be enhanced by TCC and TCC exposure would have a general anti-inflammatory effect. However, a series of recent experiments failed to show this relationship. Instead, the data generated indicated that TCC did not consistently increase the anti-inflammation-induced cytokines or chemokines in the presence of glucocorticoids, but instead indicated a modulated both pro- and anti-inflammatory cytokines and chemokines in the absence of glucocorticoids. In a subsequent series of in vitro experiments the expression of both message and protein of pro- and anti-inflammatory cytokines and chemokines were evaluated before and following the induction of an inflammatory reaction. In general, the pattern of response was to increase pro- and decrease in anti-inflammatory agents. These data change the TCC toxic-effect paradigm in two important aspects. First, the data show that the natural ligands of nuclear receptors are not required for TCC to elicit a biological action. This indicates that TCC could have effects beyond simply modulating and on-going nuclear-receptor-ligand mediate signal transduction. Second, these data suggest that TCC alone may have the ability to tip the balance of some inflammatory reactions towards a more pro-inflammatory response. Recognizing that TCC is a relative common human exposure these findings may be relevant for understanding the increase in auto-immune diseases over the past thirty years.