+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Organophosphorous pesticide metabolite (DEDTP) induces changes in the activation status of human lymphocytes by modulating the interleukin 2 receptor signal transduction pathway



Organophosphorous pesticide metabolite (DEDTP) induces changes in the activation status of human lymphocytes by modulating the interleukin 2 receptor signal transduction pathway



Toxicology and Applied Pharmacology 248(2): 122-133



Diethyldithiophosphate (DEDTP) is a metabolite formed by biotransformation of organophosphorous (OP) compounds that has a longer half-life than its parental compound. Here we evaluate the effects of DEDTP on human CD4+ T lymphocytes. In vitro exposure to DEDTP (1-50μM) decreased [(3)H]thymidine incorporation in resting cells and increased CD25 surface expression without altering cell viability. DEDTP treatment inhibited anti-CD3/anti-CD28 stimulation-induced CD4+ and CD8+ T cell proliferation determined by CFSE dilution. Decreased CD25 expression and intracellular IL-2 levels were correlated with this defect in cell proliferation. IL-2, IFN-γ and IL-10 secretion were also reduced while IL-4 secretion was not altered. Increased phosphorylation of SOCS3 and dephosphorylation of STAT5 were induced by DEDTP after as little as 5min of exposure. In addition, DEDTP induced phosphorylation of ERK, JNK and p38 and NFAT nuclear translocation. These results suggest that DEDTP can modulate phosphorylation of intracellular proteins such as SOCS3, which functions as a negative regulator of cytokine signalling, and that DEDTP exposure may thus cause T cells to fail to respond to further antigen challenges.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 054791447

Download citation: RISBibTeXText

PMID: 20659491

DOI: 10.1016/j.taap.2010.07.017


Related references

Activation of Hodgkin cells through the CD30 receptor induces interleukin-6 secretion via the NF-kappa-B transcription factor Signal transduction pathway involves the Traf-1 to -3 molecules. British Journal of Haematology 93(Suppl. 2): 175, 1996

Cyclosporin A inhibits T cell receptor-induced interleukin-2 synthesis of human T lymphocytes by selectively preventing a transmembrane signal transduction pathway leading to sustained activation of a protein kinase C isoenzyme, protein kinase C-beta. European Journal of Immunology 23(12): 3072-3081, 1993

Activation of Jak/STAT proteins involved in signal transduction pathway mediated by receptor for interleukin 2 in malignant T lymphocytes derived from cutaneous anaplastic large T-cell lymphoma and Sezary syndrome. Proceedings Of The National Academy Of Sciences Of The United States Of America. 93(17): 9148-9153, 1996

Methyl-parathion and organophosphorous pesticide metabolites modify the activation status and interleukin-2 secretion of human peripheral blood mononuclear cells. Toxicology Letters 158(1): 30-38, 2005

Differential signal transduction pathways regulating interleukin-2 synthesis and interleukin-2 receptor expression in stimulated human lymphocytes. Biochimica Et Biophysica Acta. 1235(1): 33-42, 1995

The interleukin-6 (IL-6)/IL-6-receptor system induces human chorionic gonadotropin production by activating tyrosine kinase-dependent signal transduction pathway different from pathways triggered by protein kinase activators including gonadotropin releasing hormone. Journal of Clinical Endocrinology and Metabolism 77(3): 704-709, 1993

Dual modulation of the T-cell receptor-activated signal transduction pathway by morphine in human T lymphocytes. Journal of Anesthesia 27(1): 80-87, 2013

Interleukin-6 and interleukin-11 modulate osteoblast differentiation and RANKL expression via activation of JAK-STAT signal transduction pathway. Journal of Bone & Mineral Research 17(Suppl 1): S338, 2002

Interleukin-23-induced interleukin-23 receptor subunit expression is mediated by the Janus kinase/signal transducer and activation of transcription pathway in human CD4 T cells. Journal of Interferon and Cytokine Research 31(4): 363-371, 2011

A transfected human muscarinic receptor that is coupled to the phosphatidylinositol signal transduction pathway is able to induce t cell activation. Clinical Research 38(1): 214A, 1990

Transfer of the interleukin-2 gene into human cancer cells induces specific antitumor recognition and restores the expression of CD3/T-cell receptor associated signal transduction molecules. Blood 89(1): 212-218, 1997

Activation of the Janus kinase/STAT (signal transducer and activator of transcription) signal transduction pathway by interleukin-6-type cytokines promotes osteoblast differentiation. Endocrinology 138(9): 3666-3676, 1997

The interleukin-13 receptor alpha2 chain: an essential component for binding and internalization but not for interleukin-13-induced signal transduction through the STAT6 pathway. Blood 97(9): 2673-2679, 2001

Interactions of cytochalasins and interleukin 2 on activation and signal transduction in lymphocytes from aging mice. Journal of Cell Biology 107(6 Part 3): 294A, 1988

Micrococci and peptidoglycan activate TLR2fwdarwMyD88fwdarwIRAKfwdarwTRAFfwdarwNIKfwdarwIKKfwdarwNF-kappaB signal transduction pathway that induces transcription of interleukin-8. Infection & Immunity 69(4): 2270-2276, 2001