The Transcription Factor NF-ATc1 Regulates Lymphocyte Proliferation and Th2 Cytokine Production

In recent times, human cell-based assays are gaining attention in assessments of immunomodulatory effects of chemicals. In the study here, the possible effects of cypermethrin and mancozeb on lymphocyte proliferation and proinflammatory (tumor necrosis factor (TNF-)α) and immunoregulatory cytokine (interferon- (IFN-)γ, interleukins (IL) 2, 4, 6, and 10) formationin vitrowere investigated. Human peripheral blood mononuclear cells (PBMC) were isolated and exposed for 6 hr to noncytotoxic doses (0.45–30 µM) of cypermethrin or mancozeb in the presence of activating rat S9 fraction. Cultures were then further incubated for 48 or 72 hr in fresh medium containing phytohemagglutinin (10 µg/mL) to assess, respectively, effects on cell proliferation (BrdU-ELISA method) and cytokine formation (flow cytometric bead immunoassays). Mancozeb induced dose-dependent increases in lymphocyte proliferation, inhibition of production of TNFαand theTH2 cytokines IL-6 and IL-10, and an increase in IFNγ(TH1 cytokine) production (at least 2-fold compared to control); mancozeb also induced inhibition of IL-4 (TH2) and stimulated IL-2 (TH1) production, albeit only in dose-related manners for each. In contrast, cypermethrin exposure did not cause significant effects on proliferation or cytokine profiles. Further studies are needed to better understand the functional significance of ourin vitrofindings.

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Inhibitory effects of cucurbitacin R on lymphocyte proliferation and cytokine production

Planta Medica ◽

10.1055/s-2006-949743 ◽

2006 ◽

Vol 72 (11) ◽

Author(s):

JM Escandell ◽

MC Recio ◽

R Gil ◽

I Merfort ◽

JL Ríos

Keyword(s):

Lymphocyte Proliferation ◽

Cytokine Production ◽

Inhibitory Effects

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Differential Enhancement of T Helper Type 1 (Th1)/Th2 Cytokine Production by Natural Killer T Cells Through Negative Feedback Regulation with Cytokine-conditioned Dendritic Cells

Current Immunology Reviews ◽

10.2174/157339510791111745 ◽

2010 ◽

Vol 6 (2) ◽

pp. 78-87

Author(s):

Kazuya Iwabuchi ◽

Yoshiki Yanagawa ◽

Keita Minami ◽

Kazuomi Mizuuchi ◽

Masanori Maeda ◽

...

Keyword(s):

Dendritic Cells ◽

Cytokine Production ◽

Feedback Regulation ◽

Natural Killer T Cells ◽

T Helper ◽

Negative Feedback Regulation ◽

Th2 Cytokine ◽

Killer T Cells ◽

Helper Type

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Gastric Hyperplasia and Increased Proliferative Responses of Lymphocytes in Mice Lacking the COOH-terminal Ankyrin Domain of NF-κB2

Journal of Experimental Medicine ◽

10.1084/jem.186.7.999 ◽

1997 ◽

Vol 186 (7) ◽

pp. 999-1014 ◽

Cited By ~ 128

Author(s):

Hideaki Ishikawa ◽

Daniel Carrasco ◽

Estefania Claudio ◽

Rolf-Peter Ryseck ◽

Rodrigo Bravo

Keyword(s):

T Cells ◽

Lymphocyte Proliferation ◽

Cytokine Production ◽

Cell Types ◽

Homozygous Deletion ◽

Binding Activity ◽

Activated T Cells ◽

Physiological Relevance

The nfkb2 gene encodes the p100 precursor which produces the p52 protein after proteolytic cleavage of its COOH-terminal domain. Although the p52 product can act as an alternative subunit of NF-κB, the p100 precursor is believed to function as an inhibitor of Rel/NF-κB activity by cytoplasmic retention of Rel/NF-κB complexes, like other members of the IκB family. However, the physiological relevance of the p100 precursor as an IκB molecule has not been understood. To assess the role of the precursor in vivo, we generated, by gene targeting, mice lacking p100 but still containing a functional p52 protein. Mice with a homozygous deletion of the COOH-terminal ankyrin repeats of NF-κB2 (p100−/−) had marked gastric hyperplasia, resulting in early postnatal death. p100−/− animals also presented histopathological alterations of hematopoietic tissues, enlarged lymph nodes, increased lymphocyte proliferation in response to several stimuli, and enhanced cytokine production in activated T cells. Dramatic induction of nuclear κB–binding activity composed of p52-containing complexes was found in all tissues examined and also in stimulated lymphocytes. Thus, the p100 precursor is essential for the proper regulation of p52-containing Rel/NF-κB complexes in various cell types and its absence cannot be efficiently compensated for by other IκB proteins.

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