TCDD-mediated suppression of na ïve human B cell IgM secretion involves aryl hydrocarbon receptor-mediated reduction in STAT3 serine 727 phosphorylation and is restored by Interferon-γ.

TCDD-mediated suppression of naïve human B cell IgM secretion involves aryl hydrocarbon receptor-mediated reduction in STAT3 serine 727 phosphorylation and is restored by Interferon-γ. Cell Signal. 2019 Oct 31;:109447 Authors: Blevins LK, Zhou J, Crawford R, Kaminski NE Abstract 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant formed as a byproduct in organic synthesis and burning of organic materials. TCDD has potent immunotoxic effects in B lymphocytes resulting in decreased cellular activation and suppressed IgM secretion following activation with CD40 ligand. Previous work from our lab demonstrated that TCDD treatment of naïve human B cells resulted in significant increases in the levels of the tyrosine phosphatase SHP-1, which corresponded with suppression of IgM secretion. STAT3 is a critical B cell transcription factor for B cell activation and secretion of immunoglobulins (Ig). STAT3 dimerizes and translocates to the nucleus following phosphorylation as a result of cytokine receptor signaling. We hypothesized that TCDD-mediated increases in SHP-1 could result in decreased STAT3 tyrosine phosphorylation. Interestingly, only modest changes in the levels of STAT3 tyrosine phosphorylation were observed. By contrast, TCDD significantly reduced levels of STAT3 serine phosphorylation as early as 12 h post B cell activation. These results corresponded with decreased inhibitory phosphorylation ...
Source: Cellular Signalling - Category: Cytology Authors: Tags: Cell Signal Source Type: research