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Nelson, B. Dean
Alternative names
Publications (10 of 14) Show all publications
Kretova, M., Sabova, L., Hodny, Z., Bartek, J., Kollarovic, G., Nelson, B. D., . . . Luciakova, K. (2014). TGF-beta/NF1/Smad4-mediated suppression of ANT2 contributes to oxidative stress in cellular senescence. Cellular Signalling, 26(12), 2903-2911
Open this publication in new window or tab >>TGF-beta/NF1/Smad4-mediated suppression of ANT2 contributes to oxidative stress in cellular senescence
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2014 (English)In: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 26, no 12, p. 2903-2911Article in journal (Refereed) Published
Abstract [en]

Oxidative stress and persistent activation of DNA damage response (DDR) are causally involved in the development of cellular senescence, a phenomenon implicated in fundamental (patho)physiological processes such as aging, fetal development and tumorigenesis. Here, we report that adenine nucleotide translocase-2 (ANT2) is consistently down-regulated in all three major forms of cellular senescence: replicative, oncogene-induced and drug-induced, in both normal and cancerous human cells. We previously reported formation of novel NF1/Smad transcription repressor complexes in growth-arrested fibroblasts. Here we show that such complexes form in senescent cells. Mechanistically, binding of the NF1/Smad complexes to the NF1-dependent repressor elements in the ANT2 gene promoter repressed ANT2 expression. Etoposide-induced formation of these complexes and repression of ANT2 were relatively late events co-incident with production and secretion of, and dependent on, TGF-beta. siRNA-mediated knock-down of ANT2 in proliferating cells resulted in increased levels of reactive oxygen species (ROS) and activation of the DDR. Knock-down of ANT2, together with etoposide treatment, further intensified ROS production and DNA damage signaling, leading to enhanced apoptosis. Together, our data show that TGF-beta-mediated suppression of ANT2 through NF1/Smad4 complexes contributes to oxidative stress and DNA damage during induction of cellular senescence.

Keywords
Smad, Nuclear factor 1, Senescence, Adenine nucleotide translocase-2, Transforming growth factor-beta, Oxidative stress
National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-160570 (URN)10.1016/j.cellsig.2014.08.029 (DOI)000345107700035 ()25220407 (PubMedID)
Available from: 2018-10-09 Created: 2018-10-09 Last updated: 2022-02-26Bibliographically approved
Qazi, M. R., Hassan, M., Nelson, B. D., DePierre, J. W. & Abedi-Valugerdi, M. (2013). Both sub-acute, moderate-dose and short-term, low-dose dietary exposure of mice to perfluorooctane sulfonate exacerbates concanavalin A-induced hepatitis. Toxicology Letters, 217(1), 67-74
Open this publication in new window or tab >>Both sub-acute, moderate-dose and short-term, low-dose dietary exposure of mice to perfluorooctane sulfonate exacerbates concanavalin A-induced hepatitis
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2013 (English)In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 217, no 1, p. 67-74Article in journal (Refereed) Published
Abstract [en]

Exposure of rodents to perfluorooctane sulfonate (PFOS) induces pronounced hepatomegaly associated with significant alterations in hepatic histophysiology and immune status. The present investigation was designed to evaluate the effects of this perfluorochemical on immune-mediated liver damage. Accordingly, the influence of both sub-acute (10 days), moderate-dose (0.004%, w/w = 6 +/- 1.3 mg/kg body weight/day) or short-term (28 days), low-dose (0.0001%, w/w = 144 +/- 4 mu g/kg body weight/day) dietary pretreatment with PFOS on the development of concanavalin A (Con A)-induced liver damage in mice was examined. With either regimen of exposure, PFOS exacerbated the acute liver damage caused by Con A, i.e., elevated serum levels of transaminases and led to more pronounced damage of hepatic tissue. This exacerbation was associated with either reduced (moderate dose) or unaltered (low dose) hepatic levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma). Moreover, hepatic DNA fragmentation was enhanced, particularly following short-term exposure to a low-dose. Our findings suggest that exposure to PFOS may sensitize hepatic parenchymal cells to other insults that activate the hepatic immune system and thereby exacerbate liver damage during acute inflammation.

Keywords
Concanavalin A, Pro-inflammatory cytokines, Hepatitis, Hepatomegaly, Perfluorooctane sulfonate
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:su:diva-88276 (URN)10.1016/j.toxlet.2012.12.001 (DOI)000313708000008 ()
Note

AuthorCount:5;

Available from: 2013-03-13 Created: 2013-03-12 Last updated: 2022-02-24Bibliographically approved
Qazi, M. R., Hassan, M., Nelson, B. D., DePierre, J. W. & Abedi-Valugerdi, M. (2013). Sub-acute, moderate-dose, but not short-term, low-dose dietary pre-exposure of mice to perfluorooctanoate aggravates concanavalin A-induced hepatitis. Toxicology Letters, 219(1), 1-7
Open this publication in new window or tab >>Sub-acute, moderate-dose, but not short-term, low-dose dietary pre-exposure of mice to perfluorooctanoate aggravates concanavalin A-induced hepatitis
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2013 (English)In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 219, no 1, p. 1-7Article in journal (Refereed) Published
Abstract [en]

Exposure of mice to perfluorooctanoate (PFOA) evokes pronounced hepatomegaly along with significant alterations in both the histological structure and immune status of the liver. The present study was designed to evaluate the effects of this perfluorochemical on immune-mediated liver damage. In this connection, the influence of both sub-acute (10 days), moderate-dose (0.002% w/w = 3 +/- 0.7 mg/kg body weight/day) and short-term (28 days), low-dose (0.00005% w/w = 70 +/- 2 mu g/kg body weight/day) dietary pretreatment with PFOA on the development of concanavalin A (Con A)-induced liver damage in mice was examined. With sub-acute, moderate, but not short-term, low-dose exposure, PFOA aggravated the acute liver damage caused by Con A, i.e., elevated serum levels of transaminases and led to more pronounced damage of hepatic tissue. This aggravation was associated with significantly enhanced hepatic level of interleukin-6 (IL-6), but unaltered hepatic levels of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4). Moreover, hepatic DNA fragmentation was not changed by subacute exposure to the moderate-dose. Our findings imply that exposure to PFOA may sensitize hepatic parenchymal cells to other toxicants that activate the hepatic immune system and thereby aggravate liver injury during acute inflammation. 

Keywords
Concanavalin A, Interleukin 6, Hepatitis, Hepatomegaly, Perfluorooctanoate
National Category
Biological Sciences Pharmacology and Toxicology
Identifiers
urn:nbn:se:su:diva-89853 (URN)10.1016/j.toxlet.2013.02.017 (DOI)000317348100001 ()
Note

AuthorCount:5;

Available from: 2013-05-14 Created: 2013-05-14 Last updated: 2022-02-24Bibliographically approved
Qazi, M. R., Nelson, B. D., DePierre, J. W. & Abedi-Valugerdi, M. (2012). High-dose dietary exposure of mice to perfluorooctanoate or perfluorooctane sulfonate exerts toxic effects on myeloid and B-lymphoid cells in the bone marrow and these effects are partially dependent on reduced food Consumption. Food and Chemical Toxicology, 50(9), 2955-2963
Open this publication in new window or tab >>High-dose dietary exposure of mice to perfluorooctanoate or perfluorooctane sulfonate exerts toxic effects on myeloid and B-lymphoid cells in the bone marrow and these effects are partially dependent on reduced food Consumption
2012 (English)In: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 50, no 9, p. 2955-2963Article in journal (Refereed) Published
Abstract [en]

It is well established that exposure of mice to perfluorooctanoate (PFOA) or perfluorooctane sulfonate (PFOS) exerts adverse effects on the thymus and spleen. Here, we characterize the effects of a 10-day dietary treatment with these compounds (0.001-0.02%, w/w) on the bone marrow (BM) of mice. At a dose of 0.02%, both compounds reduced food consumption and caused atrophy of the thymus and spleen. At this same dose, histopathological and flow cytometric analysis revealed that (i) the total numbers of BM as well as the numbers of myeloid, pro/pre B, immature B and early mature B cells were all reduced significantly; and (ii) these adverse effects were reversed either partially or completely 10 days after withdrawal of these compounds. At the lower dose of 0.002%, only PFOA reduced the B-lymphoid cell population. Finally, mice fed an amount of diet equivalent to that consumed by the animals exposed to 0.02% PFOA also exhibited atrophy of the thymus and spleen, and a reduction in the number of B-lymphoid population, without affecting myeloid cells. Thus, in mice, immunotoxic doses of PFOA or PFOS induce adverse effects on the myeloid and B-lymphoid cells in the BM, in part as a consequence of reduced food consumption.

Keywords
Perfluorooctane sulfonate, Perfluorooctanoate, Bone marrow, Myeloid cells, B-lymphoid cells, Food restriction
National Category
Food Science
Identifiers
urn:nbn:se:su:diva-81257 (URN)10.1016/j.fct.2012.06.023 (DOI)000308624500001 ()
Note

AuthorCount:4;

Available from: 2012-10-15 Created: 2012-10-15 Last updated: 2022-02-24Bibliographically approved
Qazi, M. R., Abedi, M. R., Nelson, B. D., DePierre, J. W. & Abedi-Valugerdi, M. (2011). Characterization of the Hepatic and Splenic Immune Status and Immunoglobulin Synthesis in Aged Male Mice Lacking the Peroxisome Proliferator-Activated Receptor-Alpha (PPAR alpha). Scandinavian Journal of Immunology, 73(3), 198-207
Open this publication in new window or tab >>Characterization of the Hepatic and Splenic Immune Status and Immunoglobulin Synthesis in Aged Male Mice Lacking the Peroxisome Proliferator-Activated Receptor-Alpha (PPAR alpha)
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2011 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 73, no 3, p. 198-207Article in journal (Refereed) Published
Abstract [en]

It is now well established that the nuclear receptor peroxisome proliferator-activated receptor-alpha (PPAR alpha) is expressed in different types of immune cells and plays a pivotal role in the regulation of age-related production of inflammatory cytokines. However, the role(s) of this receptor in the regulation of immune cell homoeostasis in ageing non-lymphoid and lymphoid organs has not yet been resolved. We examine this issue here by evaluating the hepatic and splenic immune status and immunoglobulin (Ig) production in male PPAR alpha-null mice and their wild-type littermates at one and 2 years of age. In comparison with the age-matched control animals, PPAR alpha-null mice exhibited age-related elevations in the numbers of total, as well as of phenotypically distinct subpopulations of intrahepatic immune cells (IHIC) and splenocytes. Moreover, at 2 years of age, these alterations in hepatic immune cells were accompanied by significant increases in hepatic levels of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interferon-gamma (IFN-gamma), in combination with the development of hepatic inflammatory loci containing mixtures of leucocytes. Alterations in splenocytes of old PPAR alpha-null mice were also accompanied by increases in cellularity of both white and red pulps of the spleen. Furthermore, these same animals exhibited pronounced increases in the numbers of splenic plasma cells and enhanced production of Ig of different isotypes, including IgG1, IgG2a and IgE. Thus, our findings indicate that upon ageing, PPAR alpha plays a crucial role in regulating the total numbers, compositions and functions of immune cells in both lymphoid and non-lymphoid immune organs of mice.

National Category
Immunology
Identifiers
urn:nbn:se:su:diva-67925 (URN)10.1111/j.1365-3083.2010.02495.x (DOI)000287092100003 ()
Note
authorCount :5Available from: 2012-01-02 Created: 2012-01-02 Last updated: 2022-02-24Bibliographically approved
Luciakova, K., Kollarovic, G., Kretova, M., Sabova, L. & Nelson, B. D. (2011). TGF-beta signals the formation of a unique NF1/Smad4-dependent transcription repressor-complex in human diploid fibroblasts. Biochemical and Biophysical Research Communications - BBRC, 411(3), 648-653
Open this publication in new window or tab >>TGF-beta signals the formation of a unique NF1/Smad4-dependent transcription repressor-complex in human diploid fibroblasts
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2011 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 411, no 3, p. 648-653Article in journal (Refereed) Published
Abstract [en]

We earlier reported the formation of a unique nuclear NF1/Smad complex in serum-restricted fibroblasts that acts as an NF1-dependent repressor of the human adenine nucleotide translocase-2 gene (ANT2) [K. Luciakova, G. Kollarovic, P. Barath, B.D. Nelson, Growth-dependent repression of human adenine nucleotide translocator-2 (ANT2) transcription: evidence for the participation of Smad and Sp family proteins in the NF1-dependent repressor complex, Biochem. J. 412 (2008) 123-130]. In the present study, we show that TGF-beta, like serum-restriction: (a) induces the formation of NF1/Smad repressor complexes, (b) increases binding of the complexes to the repressor elements (Go elements) in the ANT2 promoter, and (c) inhibits ANT2 expression. Repression of ANT2 by TGF-beta is eliminated by mutating the NF1 binding sites in the Go repressor elements. All of the above responses to TGF-beta are prevented by inhibitors of TGF-beta RI and MAPK p38. These inhibitors also prevent NF1/Smad4 repressor complex formation and repression of ANT2 expression in serum-restricted cells, suggesting that similar signaling pathways are initiated by TGF-beta and serum-restriction. The present finding that NF1/Smad4 repressor complexes are formed through TGF-beta signaling pathways suggests a new, but much broader, role for these complexes in the initiation or maintenance of the growth-inhibited state.

Keywords
Adenine nucleotide translocator-2, NF1, Repression, Transforming growth factor-1, p38 MAPK, TGF-beta RI
National Category
Natural Sciences
Identifiers
urn:nbn:se:su:diva-68301 (URN)10.1016/j.bbrc.2011.07.017 (DOI)000294309800030 ()
Note
authorCount :5Available from: 2012-01-13 Created: 2012-01-03 Last updated: 2022-02-24Bibliographically approved
Bogdanska, J., Borg, D., Sundström, M., Bergström, U., Halldin, K., Abedi-Valugerdi, M., . . . Nobel, S. (2011). Tissue distribution of (35)S-labelled perfluorooctane sulfonate in adult mice after oral exposure to a low environmentally relevant dose or a high experimental dose. Toxicology, 284(1-3), 54-62
Open this publication in new window or tab >>Tissue distribution of (35)S-labelled perfluorooctane sulfonate in adult mice after oral exposure to a low environmentally relevant dose or a high experimental dose
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2011 (English)In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 284, no 1-3, p. 54-62Article in journal (Refereed) Published
Abstract [en]

The widespread environmental pollutant perfluorooctane sulfonate (PFOS), detected in most animal species including the general human population, exerts several effects on experimental animals, e.g., hepatotoxicity, immunotoxicity and developmental toxicity. However, detailed information on the tissue distribution of PFOS in mammals is scarce and, in particular, the lack of available information regarding environmentally relevant exposure levels limits our understanding of how mammals (including humans) may be affected. Accordingly, we characterized the tissue distribution of this compound in mice, an important experimental animal for studying PFOS toxicity. Following dietary exposure of adult male C57/BL6 mice for 1-5 days to an environmentally relevant (0.031 mg/kg/day) or a 750-fold higher experimentally relevant dose (23 mg/kg/day) of (35)S-PFOS, most of the radioactivity administered was recovered in liver, bone (bone marrow), blood, skin and muscle, with the highest levels detected in liver, lung, blood, kidney and bone (bone marrow). Following high daily dose exposure, PFOS exhibited a different distribution profile than with low daily dose exposure, which indicated a shift in distribution from the blood to the tissues with increasing dose. Both scintillation counting (with correction for the blood present in the tissues) and whole-body autoradiography revealed the presence of PFOS in all 19 tissues examined, with identification of thymus as a novel site for localization for PFOS and bone (bone marrow), skin and muscle as significant body compartments for PFOS. These findings demonstrate that PFOS leaves the bloodstream and enters most tissues in a dose-dependent manner.

Keywords
PFOS, Distribution, Hemoglobin, Scintillation, Autoradiography, Adult mice
National Category
Biological Sciences Chemical Sciences
Identifiers
urn:nbn:se:su:diva-67584 (URN)10.1016/j.tox.2011.03.014 (DOI)000291140300008 ()
Note
authorCount :10Available from: 2011-12-29 Created: 2011-12-29 Last updated: 2022-02-28Bibliographically approved
Qazi, M. R., Nelson, B. D., DePierre, J. W. & Abedi-Valugerdi, M. (2010). 28-Day dietary exposure of mice to a low total dose (7 mg/kg) of perfluorooctanesulfonate (PFOS) alters neither the cellular compositions of the thymus and spleen nor humoral immune responses: Does the route of administration play a pivotal role in PFOS-induced immunotoxicity?. Toxicology, 267(03-jan), 132-139
Open this publication in new window or tab >>28-Day dietary exposure of mice to a low total dose (7 mg/kg) of perfluorooctanesulfonate (PFOS) alters neither the cellular compositions of the thymus and spleen nor humoral immune responses: Does the route of administration play a pivotal role in PFOS-induced immunotoxicity?
2010 (English)In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 267, no 03-jan, p. 132-139Article in journal (Refereed) Published
Abstract [en]

Short-term exposure of mice to high doses of perfluorooctanesulfonate (PFOS), an ubiquitous and highly persistent environmental contaminant, induces various metabolic changes and toxic effects, including immunotoxicity. However, extrapolation of these findings to the long-term, low-dose exposures to which humans are subject is highly problematic. In this connection, recent studies have concluded that sub-chronic (28-day) exposure of mice by oral gavage to doses of PFOS that result in serum levels comparable to those found in general human populations suppress adaptive immunity. Because of the potential impact of these findings on environmental research and monitoring, we have examined here whether sub-chronic dietary exposure (a major route of human exposure) to a similarly low-dose of PFOS also suppress adaptive immune responses. Dietary treatment of male B6C3F1 mice for 28 days with a dose of PFOS that resulted in a serum concentration of 11 mu g/ml (ppm) significantly reduced body weight gain and increased liver mass. However, this treatment did not alter the cellular compositions of the thymus and spleen; the number of splenic cells secreting IgM antibodies against sheep red blood cell (SRBC); serum levels of IgM and IgG antibodies specifically towards SRBC; or circulating levels of IgM antibodies against the T-cell-independent antigen trinitrophenyl conjugated to lipopolysaccharide (TNP-LPS). These findings indicate that such sub-chronic dietary exposure of mice to PFOS resulting in serum levels approximately 8-85-fold greater than those observed in occupationally exposed individuals does not exert adverse effects on adaptive immunity.

Keywords
Humoral immune responses, T-cell-independent antigen, T-cell-dependent antigen, Perfluorooctanesulfonate (PFOS)
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:su:diva-50059 (URN)10.1016/j.tox.2009.10.035 (DOI)000274588700017 ()
Note

authorCount :4

Available from: 2011-01-03 Created: 2010-12-21 Last updated: 2022-02-24Bibliographically approved
Qazi, M. R., Abedi, M. R., Nelson, B. D., DePierre, J. W. & Abedi-Valugerdi, M. (2010). Dietary exposure to perfluorooctanoate or perfluorooctane sulfonate induces hypertrophy in centrilobular hepatocytes and alters the hepatic immune status in mice. International Immunopharmacology, 10(11), 1420-7
Open this publication in new window or tab >>Dietary exposure to perfluorooctanoate or perfluorooctane sulfonate induces hypertrophy in centrilobular hepatocytes and alters the hepatic immune status in mice
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2010 (English)In: International Immunopharmacology, ISSN 1567-5769, E-ISSN 1878-1705, Vol. 10, no 11, p. 1420-7Article in journal (Refereed) Published
Abstract [en]

It is well established that exposure of mice to perfluorooctanoate (PFOA) or perfluorooctane sulfonate (PFOS) induces hepatomegaly and, concurrently, immunotoxicity. However, the effects of these perfluorochemicals on the histology and immune status of the liver have not been yet investigated and we have examined these issues here. Dietary treatment of male C57BL/6 mice with 0.002% (w/w) PFOA or 0.005% (w/w) PFOS for 10 days resulted in significant reductions in serum levels of cholesterol and triglycerides, a moderate increase in the serum activity of alkaline phosphatase (ALP) and hepatomegaly, without affecting other immune organs. This hepatomegaly was associated with marked hypertrophy of the centrilobular hepatocytes, with elevated numbers of cytoplasmic acidophilic granules and occasional mitosis. Furthermore, dietary exposure to PFOA or PFOS altered the hepatic immune status: whereas exposure to PFOA enhanced the numbers of total, as well as of phenotypically distinct subpopulations of intrahepatic immune cells (IHIC), and in particular the presumptive erythrocyte progenitor cells, treatment with PFOS enhanced only the numbers of hepatic cells that appear immunophenotypically to be erythrocyte progenitors, without affecting other types of IHIC. In addition, exposure to these compounds attenuated hepatic levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and interleukin-4 (IL-4). Furthermore, the exposed animals exhibited a significant increase in hepatic levels of erythropoietin, a hormone required for erythropoiesis. Thus, in mice, PFOA- and PFOS-induced hepatomegaly is associated with significant alterations in hepatic histophysiology and immune status, as well as induction of hepatic erythropoiesis.

Keywords
Perfluorooctane sulfonate, Perfluorooctanoate, Hepatomegaly, Hepatic immune system, Intrahepatic immune cells, Erythropoiesis, Erythropoietin
National Category
Natural Sciences
Research subject
Biophysics; Biochemistry
Identifiers
urn:nbn:se:su:diva-51627 (URN)10.1016/j.intimp.2010.08.009 (DOI)20816993 (PubMedID)
Available from: 2011-01-11 Created: 2011-01-11 Last updated: 2022-02-24Bibliographically approved
Qazi, M. R., Bogdanska, J., Butenhoff, J. L., Nelson, B. D., DePierre, J. W. & Abedi-Valugerdi, M. (2009). High-dose, short-term exposure of mice to perfluorooctanesulfonate (PFOS) or perfluorooctanoate (PFOA) affects the number of circulating neutrophils differently, but enhances the inflammatory responses of macrophages to lipopolysaccharide (LPS) in a similar fashion.. Toxicology, 262(3), 207-14
Open this publication in new window or tab >>High-dose, short-term exposure of mice to perfluorooctanesulfonate (PFOS) or perfluorooctanoate (PFOA) affects the number of circulating neutrophils differently, but enhances the inflammatory responses of macrophages to lipopolysaccharide (LPS) in a similar fashion.
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2009 (English)In: Toxicology, ISSN 1879-3185, Vol. 262, no 3, p. 207-14Article in journal (Refereed) Published
Abstract [en]

Having found previously that high-dose, short-term dietary exposure of mice to perfluorooctanesulfonate (PFOS) or perfluorooctanoate (PFOA) suppresses adaptive immunity, in the present study we characterize the effects of these fluorochemicals on the innate immune system. Male C57BL/6 mice receiving 0.02% (w/w) PFOS or PFOA in their diet for 10 days exhibited a significant reduction in the numbers of total white blood cells (WBC), involving lymphopenia in both cases, but neutropenia only in response to treatment with PFOA. Moreover, both compounds also markedly reduced the number of macrophages (CD11b(+) cells) in the bone marrow, but not in the spleen or peritoneal cavity. The ex vivo production of tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) by peritoneal macrophages isolated from animals treated with PFOA or PFOS was increased modestly. Moreover, both fluorochemicals markedly enhanced the ex vivo production of these same cytokines by peritoneal and bone marrow macrophages stimulated either in vitro or in vivo with lipopolysaccharide (LPS); whereas there was no such effect on splenic macrophages. The serum levels of these inflammatory cytokines observed in response to in vivo stimulation with LPS were elevated substantially by prior exposure to PFOA, but not by PFOS. None of these parameters of innate immunity were altered in animals receiving a dietary dose of these compounds that was 20-fold lower (0.001%, w/w). These findings reveal that in addition to suppressing adaptive immunity, high-dose, short-term exposure of mice to either PFOS or PFOA augments inflammatory responses to LPS, a potent activator of innate immunity.

Identifiers
urn:nbn:se:su:diva-34686 (URN)10.1016/j.tox.2009.06.010 (DOI)000269287700005 ()19540903 (PubMedID)
Available from: 2010-01-11 Created: 2010-01-11 Last updated: 2022-02-25Bibliographically approved
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