Direct effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on responses to lipopolysaccharide (LPS) by isolated murine B-cells
References (15)
- et al.
Elucidation of cellular targets responsible for tetrachlorodibenzo-p-dioxin (TCDD)-induced suppression of the antibody response. 1. Role of the B-lymphocyte
Immunopharmacology
(1988) - et al.
Direct suppression of antibody responses by chlorinated dibenzodioxins in cultured spleen cells from (C57BL/6 × C3H)F1 and DBA/2 mice
Immunopharmacology
(1986) - et al.
Effectsof 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on humoral immunity: II. B-cell activation
Immunopharmacology
(1991) - et al.
Integration of the human lymphocyte into immunotoxicological investigations
Fund Appl Toxicol
(1992) - et al.
Ia-mediated signal transduction leads to proliferation of primed B-cells
J Exp Med
(1989) - et al.
Subcompartments of the G1 phase of cell cycle detected by flow cytometry
Cell Biol
(1980) - et al.
Frequency of B-lymphocytes responsive to anti-immunoglobulin
J Exp Med
(1982)
Cited by (30)
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
2020, Cellular SignallingCitation Excerpt :AHR can bind multiple endogenous and exogenous ligands, but the persistent environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is one of the highest affinity ligands known [26]. B cells are highly sensitive targets of TCDD-mediated AHR activation as evidenced by suppressed B cell activation and function as evidenced by reduced capacity to secrete IgM and IgG [27,28]. Previous studies have reported that TCDD-mediated AHR activation results in increased expression of the Src homology phosphatase 1 (SHP-1) as well as increased BCL-6 [29].
SHP-1 is directly activated by the aryl hydrocarbon receptor and regulates BCL-6 in the presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
2016, Toxicology and Applied PharmacologyCitation Excerpt :Several studies have contributed towards identification of the molecular targets underlying TCDD-mediated suppression of the primary humoral immune response in rodents with B cell as the direct target of TCDD (Dooley and Holsapple, 1988). The specific process that TCDD impairs is the ability of B cells to differentiate into IgM-secreting plasma cells (Morris et al., 1993; Sulentic et al., 1998). Most of the toxic effects of TCDD are manifested upon diffusion into the cytosol and binding to the aryl hydrocarbon receptor (AHR) (Fernandez-Salguero et al., 1995; Vorderstrasse et al., 2001).
Cross-talk between aryl hydrocarbon receptor and the inflammatory response: A role for nuclear factor-κB
2014, Journal of Biological ChemistryCitation Excerpt :Results from EMSA and transfection assays indicate that the NF-κB-mediated increase of AhR involves elevated AhR activity. The clear increase of TCDD-induced expression of CYP1A1 by LPS in human DC as well as in thymus of B6 mice suggest that an enhanced expression of AhR during inflammation would lead to an increased sensitivity toward AhR ligands as suggested in previous reports (28–30). The reduction in both TCDD- and LPS-enhanced expression of AhR and CYP1A1 through inhibition of NF-κB indicate the importance of NF-κB in regulating the expression of AhR- and AhR-dependent genes.
Regulation of Bach2 by the aryl hydrocarbon receptor as a mechanism for suppression of B-cell differentiation by 2,3,7,8-tetrachlorodibenzo-p-dioxin
2011, Toxicology and Applied PharmacologyCitation Excerpt :Although TCDD affects multiple aspects of the immune system, cell-type fractionation reconstitution studies of heterogeneous leukocyte preparations have shown that B cells are the primary cellular targets involved in suppression of the humoral immune response (Dooley and Holsapple, 1988). Other studies have shown that direct addition of TCDD to naïve primary B cells or B-cell lines suppresses immunoglobulin M (IgM) secretion, suggesting that TCDD impairs the differentiation of B cells to IgM secreting plasma cells (Holsapple et al., 1986; Morris et al., 1993; Sulentic et al., 1998). Most of the biological effects of TCDD including the suppression of the humoral immune response are mediated through the activation of the aryl hydrocarbon receptor (AHR) (Sulentic et al., 1998; Gu et al., 2000).
Timing is everything: Consequences of transient and sustained AhR activity
2009, Biochemical PharmacologyCitation Excerpt :Yet, in the presence of a persistent exogenous agonist such as TCDD, such processes are either dampened or interrupted altogether. As a consequence, treatment with TCDD stalls proliferation and elicits a G1 arrest in multiple cell types, including hepatocytes [50,51], neuronal cells [52], thymocytes [53], and B cells [54]. The impact of AhR expression and activity on the rate of G1 passage is consistent with the idea that the receptor functions as a “throttle control” in G1 phase progression: AhR presence and transient endogenous activity promotes progression; yet when the receptor is absent or is provided with sustained agonist stimulation, movement through the cell cycle is stalled.