Effects of Possible Endocrine Disrupting Chemicals on Bacterial Component-Induced Activation of NF-.KAPPA.B

Abstract

Endocrine disrupting chemicals (EDCs) have a possibility to exacerbate infectious diseases because EDCs disturb the human immune system by interfering with endocrine balance. To assess the influence of EDCs on the innate immune function of macrophages, we investigated the effects of thirty-seven possible endocrine disruptors on lipopolysaccharide (LPS)- or bacterial lipopeptide (Pam3CSK4)-induced activation of nuclear factor kappa B (NF-kappaB). Alachlor, benomyl, bisphenol A, carbaryl, kelthane, kepone, octachlorostyrene, pentachlorophenol, nonyl phenol, p-octylphenol and ziram inhibited both LPS- and Pam3CSK4-induced activation of NF-kappaB. Simazine inhibited only LPS-induced activation. A strong inhibitory effect was observed with ziram and benomyl. On the other hand, diethylhexyl adipate and 4-nitrotoluene tended to enhance the activation induced by Pam3CSK4 and LPS, respectively. Aldicarb, amitrole, atrazine, benzophenone, butyl benzyl phthalate, 2,4-dichlorophenoxy acetic acid, dibutyl phthalate, 2,4-dichlorophenol, dicyclohexyl phthalate, diethylhexyl phthalate, diethyl phthalate, dihexyl phthalate, di-n-pentyl phthalate, dipropyl phthalate, malathion, methomyl, methoxychlor, metribuzin, nitrofen, permethrin, trifluralin, 2,4,5-trichlorophenoxyacetic acid and vinclozolin had no significant effects at 100 microM. These results indicate that some agrochemicals have the potential to inhibit macrophage function and suggest that endocrine disruptors may influence the development of bacterial infections.