Extracellular signal-regulated kinases 1/2 and Akt contribute to triclosan-stimulated proliferation of JB6 Cl 41-5a cells

Abstract

Triclosan is a broad spectrum anti-bacterial agent widely used in many personal care products, household items, medical devices, and clinical settings. Human exposure to triclosan is mainly through oral and dermal routes. In previous studies, we found that sub-chronic dermal exposure of B6C3F1 mice to triclosan induced epidermal hyperplasia and focal necrosis; however, the mechanisms for these responses remain elusive. In this study, using mouse epidermis-derived JB6 Cl 41-5a cells, we found that triclosan stimulated cell growth in a concentration- and time-dependent manner. Enhanced cell proliferation was demonstrated by a substantial increase in the percentage of BrdU-positive cells, an elevation in the protein levels of cyclin D1 and cyclin A, and a reduction in the protein level of p27(Kip1). Western blotting analysis revealed that triclosan induced the activation of extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK), p38, and Akt. Pre-treatment of the cells with PD184352, an inhibitor of the upstream kinase MEK1/2, or with wortmannin, an inhibitor of phosphoinositide 3-kinase, blocked triclosan-mediated phosphorylation of ERK1/2 and Akt, respectively, and substantially suppressed triclosan-stimulated cell proliferation, whereas the JNK inhibitor SP600125 or the p38 inhibitor SB203580 had little to no effect on triclosan-stimulated cell proliferation. The phosphorylation activation of ERK1/2 and Akt was further confirmed on the skin of mice dermally administered triclosan. These data suggest that the activation of ERK1/2 and Akt is involved in triclosan-stimulated proliferation of JB6 Cl 41-5a cells.

Reactive oxygen species and c-Jun N-terminal kinases contribute to TEMPO-induced apoptosis in L5178Y cells

“…It is known that ROS initiates apoptosis and activates various signaling pathways, with the cascaded reactions and crosstalk among multiple cellular events contributing to toxicity associated with certain chemicals [25,[48][49][50][51][52][53][54]. In this present study, we found that two members of the MAPK signaling pathway, JNK and p38, were activated at high and moderate levels, respectively (Fig.…”

Triclosan: An Update on Biochemical and Molecular Mechanisms

“…In agreement with the cytotoxicity data, TCS-treated mouse lung epithelial cells were deformed with reduced viability [83]. Conversely, TCS stimulated the proliferation of mouse epidermis-derived JB6 Cl 41-5a cells, by increasing cyclins D1 and A and reducing p27(Kip1) protein levels [84]. Examining these effects in vivo , B6C3F1 mice exhibited epidermal hyperplasia and focal necrosis following topical administration of TCS.…”

P38/TRHr-Dependent Regulation of TPO in Thyroid Cells Contributes to the Hypothyroidism of Triclosan-Treated Rats

“…However, effects of triclosan on the MAPK pathway vary from different studies. In JB6 Cl 41-5a cells, triclosan at 3 µM stimulated cell proliferation via activating the ERK and Akt pathways, but not the p38 pathway [18]; in neural stem cells, triclosan at 50 µM decreased the cell viability through inducing the phosphorylation of p38 and JNK [15]. We analyze that the diverse effects of triclosan on the MAPK pathway maybe consist in different cells and various concentrations used.…”