Superfund Research Program
TCDD Impedes the Minimal Activation Threshold Required for Initiation of B Cell Differentiation: An Integrated Experimental and Computational Modeling Approach
Project Leader: Norbert E. Kaminski
Grant Number: P42ES004911
Funding Period: 2000-2021
Project-Specific Links
Publications
2022
- Zhou J, Blevins L, Crawford RB, Kaminski NE. 2022. Role of programmed cell death protein-1 and lymphocyte specific protein tyrosine kinase in the aryl hydrocarbon receptor- mediated impairment of the IgM response in human CD5(+) innate-like B cells. Front Immunol doi:10.3389/fimmu.2022.884203 PMID:35558082 PMCID:PMC9088000
2021
- Blevins L, Zhou J, Crawford RB, Kaminski NE. 2021. Identification of a sensitive human immunological target of aryl hydrocarbon receptor activation: CD5+ innate-like B cells. Front Immunol 12:635748. doi:10.3389/fimmu.2021.635748 PMID:33936048 PMCID:PMC8082145
- Williams MR, Stedtfeld RD, Stedtfeld TM, Crawford RB, Kuwahara T, Kaminski NE, Tiedje JM, Hashsham SA. 2021. MicroRNA-based host response to toxicant exposure is influenced by the presence of gut microbial populations. Sci Total Environ 797:doi:10.1016/j.scitotenv.2021.149130 PMID:34311349 PMCID:PMC8464502
- Yuan Q, Sallach JB, Rhodes G, Bach A, Crawford RB, Li H, Johnston CT, Teppen BJ, Kaminski NE, Boyd SA. 2021. Natural organic matter does not diminish the mammalian bioavailability of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Chemosphere 264(Pt1):128420. doi:10.1016/j.chemosphere.2020.128420 PMID:33032214 PMCID:PMC7749823 (ahead of print)
2020
- Blevins L, Zhou J, Crawford RB, Kaminski NE. 2020. TCDD-mediated suppression of naive human B cell IgM secretion involves aryl hydrocarbon receptor-mediated reduction in STAT3 serine 727 phosphorylation and is restored by interferon-y. Cell Signal 65:109447. doi:10.1016/j.cellsig.2019.109447 PMID:31678681 PMCID:PMC6903688
2019
- Josyula N, Andersen ME, Kaminski NE, Dere E, Zacharewski TR, Bhattacharya S. 2019. Gene co-regulation and co-expression in the aryl hydrocarbon receptor-mediated transcriptional regulatory network in the mouse liver. Arch Toxicol 94:113-126. doi:10.1007/s00204-019-02620-5 PMID:31728591
- Sallach JB, Crawford RB, Li H, Johnston CT, Teppen BJ, Kaminski NE, Boyd SA. 2019. Activated carbons of varying pore structure eliminate the bioavailability of 2,3,7,8-tetrachlorodibenzo-p-dioxin to a mammalian (mouse) model. Sci Total Environ 650:2231-2238. doi:10.1016/j.scitotenv.2018.09.270
- Zhang Q, Caudle W, Pi J, Bhattacharya S, Andersen ME, Kaminski NE, Conolly RB. 2019. Embracing systems toxicology at single-cell resolution. Curr Opin Toxicol 16:49-57. doi:10.1016/j.cotox.2019.04.003 PMID:31768481 PMCID:PMC6876623
2018
- Dornbos P, Warren M, Crawford RB, Kaminski NE, Threadgill DW, LaPres JJ. 2018. Characterizing Serpinb2 as a modulator of TCDD-induced suppression of the B cell. Chem Res Toxicol 31(11):1248-1259. doi:10.1021/acs.chemrestox.8b00225 PMID:30339366 (ahead of print)
- Zhou J, Henriquez J, Crawford RB, Kaminski NE. 2018. Suppression of the IgM response by aryl hydrocarbon receptor activation in human primary B cells involves impairment of immunoglobulin secretory processes. Toxicol Sci 163(1):doi:10.1093/toxsci/kfy036 PMID:29462421 (ahead of print)
- Zhou J, Zhang Q, Henriquez J, Crawford RB, Kaminski NE. 2018. Lymphocyte-specific protein tyrosine kinase (LCK) is involved in the aryl hydrocarbon receptor-mediated impairment of immunoglobulin secretion in human primary B cells. Toxicol Sci 165(2):322-334. doi:10.1093/toxsci/kfy133 PMID:29860352
2017
- Boyd SA, Sallach JB, Zhang Y, Crawford RB, Li H, Johnston CT, Teppen BJ, Kaminski NE. 2017. Sequestration of 2,3,7,8-tetrachlorodibenzo-p-dioxin by activated carbon eliminates bioavailability and the suppression of immune function in mice. Environ Toxicol Chem 36(10):2671-2678. doi:10.1002/etc.3815 PMID:28370362
- Henriquez J, Zhou J, Li J, Crawford RB, Kaminski NE. 2017. Application of gene specific mRNA level determinations in individual cells using flow cytometry-based PrimeFlow (TM) in immunotoxicology. Toxicol Appl Pharmacol 337:39-44. doi:10.1016/j.taap.2017.10.021 PMID:29107001 PMCID:PMC5718209
- Kovalova N, Nault R, Crawford RB, Zacharewski TR, Kaminski NE. 2017. Comparative analysis of TCDD-induced AhR-mediated gene expression in human, mouse and rat primary B cells. Toxicol Appl Pharmacol 316:95-106. doi:10.1016/j.taap.2016.11.009 PMID:27913140 PMCID:PMC5292778
- Phadnis-Moghe AS, Kaminski NE. 2017. Immunotoxicity testing using human primary leukocytes: an adjunct approach for the evaluation of human risk. Curr Opin Toxicol 3:25-29. doi:10.1016/j.cotox.2017.04.005 PMID:29619412 PMCID:PMC5880284
- Stedtfeld RD, Chai B, Crawford RB, Stedtfeld TM, Williams MR, Xiangwen S, Kuwahara T, Cole JR, Kaminski NE, Tiedje JM, Hashsham SA. 2017. Modulatory influence of segmented filamentous bacteria on transcriptomic response of gnotobiotic mice exposed to TCDD. Front Microbiol 8:12. doi:10.3389/fmicb.2017.01708 PMID:28936204 PMCID:PMC5594080
- Stedtfeld RD, Sallach JB, Crawford RB, Stedtfeld TM, Williams MR, Waseem H, Johnston CT, Li H, Teppen BJ, Kaminski NE, Boyd SA, Tiedje JM, Hashsham SA. 2017. TCDD administered on activated carbon eliminates bioavailability and subsequent shifts to a key murine gut commensal. Appl Microbiol Biotechnol 101:7409-7415. doi:10.1007/s00253-017-8460-9 PMID:28812142
2016
- Kovalova N, Manzan MA, Crawford RB, Kaminski NE. 2016. Role of aryl hydrocarbon receptor polymorphisms on TCDD-mediated CYP1B1 induction and IgM suppression by human B cells. Toxicol Appl Pharmacol 309:15-23. doi:10.1016/j.taap.2016.08.011 PMID:27535091 PMCID:PMC5035641
- Phadnis-Moghe AS, Li J, Crawford RB, Kaminski NE. 2016. 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). Toxicol Appl Pharmacol 310:41-50. doi:10.1016/j.taap.2016.08.014 PMID:27546522 PMCID:PMC5064869
2015
- Fader KA, Nault R, Ammendolia DA, Harkema JR, Williams KJ, Crawford RB, Kaminski NE, Potter D, Sharratt B, Zacharewski TR. 2015. 2,3,7,8-Tetrachlorodibenzo-p-dioxin alters lipid metabolism and depletes immune cell populations in the jejunum of C57BL/6 mice. Toxicol Sci 148(2):567-580. doi:10.1093/toxsci/kfv206 PMID:26377647 PMCID:PMC5009443
- Phadnis AS, Crawford RB, Kaminski NE. 2015. Suppression of human B cell activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin involves altered regulation of B cell lymphoma-6. Toxicol Sci 144(1):39-50. doi:10.1093/toxsci/kfu257 PMID:25543051 PMCID:PMC4349138
2014
- Ye W, Paul D, Gao L, Seckute J, Sangaiah R, Jayaraj K, Zhang Z, Kaminski P, Ealick SE, Gold A, Ball LM. 2014. Ethenoguanines undergo glycosylation by nucleoside 2'-deoxyribosyltransferases at non-natural sites. PLoS One 9(12):e115082. doi:10.1371/journal.pone.0115082 PMID:25521390 PMCID:PMC4270796
2013
- Zhang Q, Kline DE, Bhattacharya S, Crawford RB, Conolly RB, Thomas RS, Andersen ME, Kaminski NE. 2013. All-or-none suppression of B cell terminal differentiation by environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Appl Pharmacol 268(1):17-26. doi:10.1016/j.taap.2013.01.015 PMID:23357550 PMCID:PMC3594464
2011
- De Abrew KN, Phadnis AS, Crawford RB, Kaminski NE, Thomas RS. 2011. 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. Toxicol Appl Pharmacol 252(2):150-158. doi:10.1016/j.taap.2011.01.020 PMID:21296099 PMCID:PMC3106294
- Kaplan BL, Crawford RB, Kovalova N, Arencibia A, Kim S, Pinnavaia TJ, Boyd SA, Teppen BJ, Kaminski NE. 2011. TCDD adsorbed on silica as a model for TCDD contaminated soils: evidence for suppression of humoral immunity in mice. Toxicology 282(3):82-87. doi:10.1016/j.tox.2011.01.013 PMID:21272611 PMCID:PMC3089373
- Lu H, Crawford RB, Kaplan BL, Kaminski NE. 2011. 2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated disruption of the CD40 ligand-induced activation of primary human B cells. Toxicol Appl Pharmacol 255:251-260. doi:10.1016/j.taap.2011.06.026 PMID:21807014 PMCID:PMC3189629
- McClure EA, North CM, Kaminski NE, Goodman JI. 2011. Changes in DNA methylation and gene expression during 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced suppression of the lipopolysaccharide-stimulated IgM response in splenocytes. Toxicol Sci 120(2):339-348. doi:10.1093/toxsci/kfq396 PMID:21212295 PMCID:PMC3061478
- Sulentic CE, Kaminski NE. 2011. The long winding road toward understanding the molecular mechanisms for B cell suppression by 2,3,7,8-Tetrachlorodibenzo-p-dioxin. Toxicol Sci 120(suppl1):S171-S191. doi:10.1093/toxsci/kfq324 PMID:20952503 PMCID:PMC3043085
2010
- Bhattacharya S, Conolly RB, Kaminski NE, Thomas RS, Andersen ME, Zhang Q. 2010. A bistable switch underlying B-cell differentiation and its disruption by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Sci 115(1):51-65. doi:10.1093/toxsci/kfq035 PMID:20123757 PMCID:PMC2855357
- Crawford RB, Kaminski NE, Lu H, North CM. 2010. 2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated suppression of toll-like receptor stimulated B-lymphocyte activation and initiation of plasmacytic differentiation. Toxicol Sci 116:99-112. doi:10.1093/toxsci/kfq095 PMID:20348231 PMCID:PMC2886857
- De Abrew KN, Kaminski NE, Thomas RS. 2010. An integrated genomic analysis of aryl hydrocarbon receptor-mediated inhibition of B-cell differentiation. Toxicol Sci 118(2):454-469. doi:10.1093/toxsci/kfq265 PMID:20819909 PMCID:PMC3003543
- De Abrew KN, Kaminski NE, Thomas RS. 2010. Identification of direct AhR-regulated genes involved in B cell differentiation. The Toxicologist 99 (Abst. 1195).
- Kline DE, Zhang Q, Bhattacharya S, Andersen ME, Conolly RB, Crawford RB, Kaminski NE. 2010. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) Suppresses LPS-activated Binary Switching of B Cells to Plasma Cells.
- Lu H, Crawford RB, Suarez-Martinez J, Kaplan BL, Kaminski NE. 2010. Induction of the aryl hydrocarbon receptor-responsive genes and modulation of the immunoglobulin M response by 2,3,7,8-tetrachlorodibenzo-p-dioxin in primary human B cells. Toxicol Sci 118(1):86-97. doi:10.1093/toxsci/kfq234 PMID:20702590 PMCID:PMC2955211
- Lu H, Kaplan BL, Crawford RB, Kaminski NE. 2010. Characterization of 2,3,7,8-tetrachlorodibenzo-pdioxin Effect on the CD40L-Induced IgM Antibody Responses in Primary Mouse and Human B Lymphocytes. The Toxicologist 99 (Abst. 1533).
- North CM, Crawford RB, Lu H, Kaminski NE. 2010. Multiparametric single cell analysis of toll-like receptor activated kinase phosphorylation alteration by 2,3,7,8-Tetrachlorodibenzo-p-dioxin. The Toxicologist 99 (Abst. 632).
- Phadnis AS, Manzan MA, Thomas RA, Kaminski NE. 2010. Direct regulation of Bach2 by 2,3,7,8- Tetrachlorodibenzo-p-dioxin in B lymphoma CH12.LX. The Toxicologist 99 (Abst. 73).
- Zhang Q, Bhattacharya S, Kline DE, Crawford RB, Thomas RS, Kaminski NE, Andersen ME, Conolly RB. 2010. Stochastic modeling of B lymphocyte terminal differentiation and its suppression by dioxin. BMC Syst Biol 4:40. doi:10.1186/1752-0509-4-40 PMID:20359356 PMCID:PMC2859749
2009
- Crawford RB, North CM, Kaplan BL, Kaminski NE, Lu H. 2009. Establishment of an immunoglobulin m antibody-forming cell response model for characterizing immunotoxicity in primary human B cells. Toxicol Sci 112(2):363-373. doi:10.1093/toxsci/kfp224 PMID:19767444 PMCID:PMC2777081
- North CM, Crawford RB, Kaminski NE, Lu H. 2009. Simultaneous in vivo time course and dose response evaluation for TCDD-induced impairment of the LPS-stimulated primary IgM response. Toxicol Sci 112(1):123-132. doi:10.1093/toxsci/kfp187 PMID:19675145 PMCID:PMC2769062
- North CM, Kim B, Snyder N, Crawford RB, Holsapple MP, Kaminski NE. 2009. TCDD-mediated suppression of the in vitro anti-sheep erythrocyte IgM antibody forming cell response is reversed by interferon-gamma. Toxicol Sci 107(1):85-92. doi:10.1093/toxsci/kfn223 PMID:18948302 PMCID:PMC2638643
- Schneider D, Yoo B, Kaminski NE. 2009. Involvement of Blimp-1 and AP-1 dysregulation in the 2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated suppression of the IgM response by B cells. Toxicol Sci 108(2):377-388. doi:10.1093/toxsci/kfp028 PMID:19237549 PMCID:PMC2664693
2008
- Schneider D, Manzan MA, Crawford RB, Chen W, Kaminski NE. 2008. 2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated impairment of B cell differentiation involves dysregulation of paired box 5 (Pax5) isoform, Pax5a. J Pharmacol Exp Ther 326(2):463-474. doi:10.1124/jpet.108.139857 PMID:18483191 PMCID:PMC2562000
2007
- Shnaider D, Byung SY, Kaminski NE. 2007. A putative role for Blimp-1 and AP-1 in TCDD-induced suppression of the IgM response in B cells. Environ Health Perspect 96(1):(Abst.828).
2006
- Learn CA, Kaminski NE, Thomas RS. 2006. Modulation of the B-Cell immunologic program by superfund halogenated aromatic hydrocarbons. In: Superfund Basic Research Program Annual Meeting, December 11-12. La Jolla, CA.
- Shnaider D, Yoo BS, Kaminski NE. 2006. Blimp-1 and Pax5 are involved in the suppression of B-Cell differentiation by TCDD. In: Superfund Basic Research Program Annual Meeting, December 11-12. La Jolla, CA.
- Zhang Q, Thomas RS, Kaminski NE, Conolly RB, Andersen ME. 2006. Computational modeling of TCDD disruption of B-cell terminal differentiation. In: Superfund Basic Research Program Annual Meeting, December 11-12. La Jolla, CA.
2004
- Boverhof DR, Tam E, Harney AS, Crawford RB, Kaminski NE, Zacharewski TR. 2004. 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces suppressor of cytokine signaling 2 in murine B cells. Mol Pharmacol 66(6):1662-1670. PMID:15371557
- Boverhof DR, Tam E, Harney AS, Crawford RB, Kaminski NE, Zacharewski TR. 2004. Suppressor of cytokine signaling-2: a novel TCDD inducible gene in CH12.LX murine B-cells. Environ Health Perspect 78(1-S):(Abst.1412).
- Linning KD, Tai M, Madhukar BV, Chang C, Reed DN, Ferber S, Trosko JE, Olson LK. 2004. Redox-mediated enrichment of self-renewing adult human pancreatic cells that possess endocrine differentiation potential. Pancreas 29(3):E64-E76. PMID:15367896
- Madhukar BV, Chen G, Wood BF. 2004. PCB activation of extracellular signal-regulated kinases (ERKs) is mediated through epidermal growth factor receptor and intracellular calcium. Environ Health Perspect 78(S-1):Abst.1170.
- McKarns SC, Schwartz RH, Kaminski NE. 2004. Smad3 is essential for TGF-beta 1 to suppress IL-2 production and TCR-induced proliferation, but not IL-2-induced proliferation. J Immunol 172(7):4275-4284. PMID:15034041
2003
- Bezdecny SA, Roth RA, Ganey PE. 2003. Expression of cyclooxygenase-2 in HL-60 cells exposed to polychlorinated biphenyls. Toxicol Sci 72(1):1571Suppl.S..
- Madhukar BV, Hernandez-Maldonado O. 2003. A diorthochlorinated PCB congener 2,2 ',4,4 '-tetrachlorobiphenyl (TCB) activates extracellular signal regulated kinases (ERKs) independent of protein kinase C (PKC) in JB6 mouse epidermal cells. Toxicol Sci 72(1):1574Suppl.S.
- McKarns SC, Letterio JJ, Kaminski NE. 2003. Concentration-dependent bifunctional effect of TGF-beta(1) on immunoglobulin production: a role for Smad3 in IgA production in vitro. Int Immunopharmacol 3(13-14):1761-1774. PMID:14636827
- Suh J, Kang J, Yang K, Kaminski NE. 2003. Antagonism of aryl hydrocarbon receptor-dependent induction of CYP1A1 and inhibition of IgM expression by di-ortho-substituted polychlorinated biphenyls. Toxicol Appl Pharmacol 187(1):11-21. PMID:12628580
- Sulentic CE, Na YJ, Fintushel S, Kaminski NE. 2003. Transcriptional regulation of the hs4 domain through a DRE and kappaB motif. Environ Health Perspect 72(1-S):1780.
- Tai M, Olson LK, Madhukar BV, Linning KD, Van Camp LL, Tsao M, Trosko JE. 2003. Characterization of gap junctional intercellular communication in immortalized human pancreatic ductal epithelial cells with stem cell characteristics. Pancreas 26(1):e18-e26. PMID:12499933
2002
- Madhukar BV, Hernandez-Maldonado O. 2002. Di-ortho chlorine substituted PCB congeners activate mitogen-activated protein kinases independent of protein kianse C activation in JB-6 mouse epidermal cells. In: SOT 41st Annual Meeting.
- Na YJ, Sulentic CE, Yang K, Holsapple MP, Kaminski NE. 2002. Non-coplanar polychlorinated biphenyl (PCB) congeners inhibit PCB 126-induced activation of the 3'alpha enhancer in lipopolysaccharide-stimulated CH12.LX B-cells. Environ Health Perspect 66(1-S):
- Olivero J, Bezdecny SA, Ganey PE. 2002. A molecular motif required for the activation of rat neutrophil Phospholipase A2 by organochlorine compounds. Chem Res Toxicol 15(2):153-159.
- Suh J, Jeon YJ, Kim HM, Kang J, Kaminski NE, Yang K. 2002. Aryl hydrocarbon receptor-dependent inhibition of AP-1 activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated B cell dysfunction. Toxicol Appl Pharmacol 181(2):116-123.
- Sulentic CE, Na YJ, Oestreich JH, Holsapple MP, Kaminski NE. 2002. 2,3,7,8-tetrachlorodibenzo-p-dioxin inhibits transcriptional activity of the 3'alpha enhancer in lipopolysaccharide-stimulated CH12.LX B-cells. Environ Health Perspect 66(1-S):
- Villeneuve DL, Khim JS, Kannan K, Giesy JP. 2002. Relative potencies of individual polycyclic aromatic hydrocarbons to induce dioxinlike and estrogenic responses in three cell lines. Environ Toxicol Chem 17:128-137. PMID:11979591
- Villeneuve DL, Villalobos SA, Keith TL, Snyder EM, Fitzgerald SD, Giesy JP. 2002. Effects of waterborne exposure to 4-nonylphenol on plasma sex steroid and vitellogenin concentrations in sexually mature male carp (Cyprinus carpio). Chemosphere 47(1):15-28. PMID:11996132
- Wang XQ, Fang J, Nunez AA, Clemens LG. 2002. Developmental exposure to polychlorinated biphenyls affects sexual behavior of rats. Physiol Behav 75(5):689-696. PMID:12020734
2001
- Olivero J, Ganey PE. 2001. Participation of Ca2+/calmodulin during activation of rat neutrophils by polychlorinated biphenyls. Biochem Pharmacol 62:1125-1132. PMID:11597581
- Ruch RJ, Trosko JE, Madhukar BV. 2001. Inhibition of connexin43 gap junctional intercellular communication by TPA requires ERK activation. J Cell Biochem 83(1):163-169. PMID:11500965
2000
- Ganey PE, Olivero-Verbal J, Madhukar BV. 2000. Mechanism of inhibition of stimulated neutrophil degranulation by 2,2',4,4'-tetrachlorobiphenyl. Toxicol Sci 54:77.
- McKarns SC, Kaminski NE. 2000. Evidence for a role by SMADS in TGF-1-induced modulation of T-cell effector function. Environ Health Perspect 54:303.
- Olivero-Verbal J, Ganey PE. 2000. A common elecrotopological motif among organochlorine compounds that activate neutrophils. Toxicol Sci 54:77.
- Suh J, Kang J, Yang K, Kaminski NE. 2000. Antagonistic effects of di-ortho polychlorinated biphenyls on aryl hydrocarbon receptor-dependent CYP1A1 and IgM gene expressions in CH12.LX B cells. Environ Health Perspect 54:279.