HIV-1 Nef Inhibits Lipopolysaccharide-induced IL-12p40 Expression by Inhibiting JNK-activated NFκB in Human Monocytic Cells
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Post-publication record
- Nature
- Retraction
- Reason
- Investigation by Company/Institution;Manipulation of Images;Notice - Limited or No Information;
- Date
- 1/2/2012 0:00
- Flagged by OpenAlex?
- Yes
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Abstract
Impaired cellular immunity caused by decreased production of Th1-type cytokines, including interleukin-12 (IL-12) is a major feature of HIV-1-associated immunodeficiency and acquired immunodeficiency syndrome. IL-12p40, an inducible subunit shared between IL-12 and IL-23, plays a critical role in the development of cellular immunity, and its production is significantly decreased during HIV infection. The mechanism by which HIV induces loss of IL-12p40 production remains poorly understood. We have previously shown that lipopolysaccharide (LPS)-induced IL-12p40 production in monocytic cells is regulated by NFkappaB and AP-1 transcription factors through the activation of two distinct upstream signaling pathways, namely the c-Jun-N-terminal kinase (JNK) and the calmodulin-dependent protein kinase-II-activated pathways. Herein, we show that intracellular nef expressed through transduction of primary monocytes and promonocytic THP-1 cells with retroviral-mediated nef gene inhibited LPS-induced IL-12p40 transcription by inhibiting the JNK mitogen-activated protein kinases without affecting the calmodulin-dependent protein kinase-II-activated pathway. In addition, nef inhibited JNK-activated NFkappaB without affecting the AP-1 activity. Overall, our results suggest for the first time that intracellular nef inhibited LPS-activated JNK, which may cause inhibition of IL-12p40 expression in human monocytic cells by selectively inhibiting NFkappaB activity.
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The record
- Venue
- Journal of Biological Chemistry
- Topic
- NF-κB Signaling Pathways
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- Ottawa HospitalChildren's Hospital of Eastern OntarioUniversity of Ottawa
- Funders
- —
- Keywords
- Cell biologyKinaseSignal transductionBiologyProtein kinase ANF-κBIntracellularNFKB1Transcription factorGeneBiochemistry
- Has abstract in OpenAlex
- yes