HIV‐1 Tat protein induces interleukin‐10 in human peripheral blood monocytes: involvement of protein kinase C‐βII and ‐δ

2002 ◽  
Vol 16 (6) ◽  
pp. 546-554 ◽  
Author(s):  
Yamina Bennasser ◽  
Elmostafa Bahraoui
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Interleukin 10 ◽  
Tat Protein ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Kinase C ◽  
Hiv 1

scholarly journals Tat Protein of Human Immunodeficiency Virus Type 1 Induces Interleukin-10 in Human Peripheral Blood Monocytes: Implication of Protein Kinase C-Dependent Pathway

2000 ◽  
Vol 74 (22) ◽  
pp. 10551-10562 ◽  
Author(s):  
Abdallah Badou ◽  
Yamina Bennasser ◽  
Marc Moreau ◽  
Catherine Leclerc ◽  
Monsef Benkirane ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Interleukin 10 ◽  
Tat Protein ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Kinase C ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The clinical manifestations observed in human immunodeficiency virus type 1 (HIV-1)-infected patients are primarily due to the capacity of the virus and its components to inactivate the immune system. HIV-1 Tat protein could participate in this immune system disorder. This protein is secreted by infected cells of HIV-infected patients and is free in the plasma, where it can interact and be taken up by both infected and noninfected cells. In asymptomatic patients infected by HIV-1, production of interleukin-10 (IL-10), a highly immunosuppressive cytokine, is associated with disease progression to AIDS. In the present work, we tested the capacity of Tat to induce IL-10 production by peripheral blood monocytes of healthy donors. The results show that Tat causes the production of IL-10 in a dose- and stimulation time-dependent manner. Investigations of the mechanisms involved in signal transduction show that (i) the calcium pathway is not or only slightly involved in Tat-induced IL-10 production, (ii) the protein kinase C pathway plays an essential role, and (iii) monocyte stimulation by Tat results in the intranuclear translocation of transcription factor NF-κB and in the induction of phosphorylation of the mitogen-activated protein kinases ERK1 and ERK2; activation of these two potential substrates of protein kinase C is required for the production of IL-10. Finally, our results suggest that the effect of Tat is exerted at the membrane level and that the active domain is located within N-terminal residues 1 to 45. This production of IL-10 induced by Tat could participate in the progression of HIV infection to AIDS.

scholarly journals A Novel Protein Kinase C (PKCϵ) Is Required for fMet-Leu-Phe-induced Activation of NF-κB in Human Peripheral Blood Monocytes

2005 ◽  
Vol 280 (23) ◽  
pp. 22497-22501 ◽  
Author(s):  
Ling-Yu Chen ◽  
Astrid Doerner ◽  
Paul F. Lehmann ◽  
Shuang Huang ◽  
Guangming Zhong ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Peripheral Blood ◽  
Rho Gtpase ◽  
Human Peripheral Blood ◽  
Small Gtpase ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Kinase C ◽  
Novel Protein

We have reported that the chemoattractant, fMet-Leu-Phe (fMLP), induces the activation of NF-κB in human peripheral blood monocytes and that this requires the activity of small GTPase, RhoA (Huang, S., Chen, L.-Y., Zuraw, B. L., Ye, R. D., and Pan, Z. K. (2001) J. Biol. Chem. 276, 40977-40981). Here we showed that the novel protein kinase C isozyme, PKCϵ, associates functionally with RhoA in fMLP-stimulated monocytes and that PKCϵ acted as a signaling component downstream of the GTPase RhoA during fMLP-induced activation of NF-κB. Stimulation of monocytes with fMLP resulted in activation of both PKCϵ and NF-κB. This latter activation was largely blocked by specific inhibitors of PKCϵ by transient expression of a dominant-negative form of PKCϵ and by PKCϵ-specific short interfering RNA. These findings demonstrate, for the first time, that fMLP-induced activation of NF-κB utilizes a signaling pathway, which requires activity of PKCϵ, and that PKCϵ acts as a signaling component downstream of RhoA in cytokine gene transcription stimulated by a chemoattractant. The specificity of this response suggests an important role for the Rho GTPase-PKCϵ-NF-κB pathway in host defense and represents a novel and potentially important mechanism through which fMLP not only attracts leukocytes but may also contribute directly to inflammation.

RANTES inhibits HIV-1 replication in human peripheral blood monocytes and alveolar macrophages

1997 ◽  
Vol 272 (5) ◽  
pp. L1025-L1029 ◽  
Author(s):  
M. J. Coffey ◽  
C. Woffendin ◽  
S. M. Phare ◽  
R. M. Strieter ◽  
D. M. Markovitz
Keyword(s):  
T Lymphocytes ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Mononuclear Phagocytes ◽  
Dependent Manner ◽  
Blood Monocytes ◽  
Hiv Replication ◽  
Peripheral Blood Monocytes ◽  
Cd8 T Lymphocytes ◽  
Hiv 1

Infection with human immunodeficiency virus (HIV)-1 most often leads to the development of acquired immune deficiency syndrome, which may manifest with opportunistic infections, many of which occur in the lung. Mononuclear phagocytes infected by HIV-1, being relatively resistant to its cytopathic effects, potentially act as a reservoir for the virus. The alveolar macrophage (AM), a differentiated lung tissue macrophage, is readily infected by HIV-1, after which the virus becomes relatively dormant. C-C chemokines, secreted by CD8 T lymphocytes and other cells, are known to suppress HIV replication in lymphocytes. In view of this observation, and the relative increase in CD8+ T lymphocytes during HIV-1 disease, particularly in the lung, we hypothesized that C-C chemokines might play a key role in suppressing HIV-1 replication in AM. We examined the effect of the C-C chemokines macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and regulated on activation normal T cell expressed and secreted (RANTES) singly and in combination on HIV-1 replication in peripheral blood monocytes (PBM) and AM infected in vitro. Our findings indicate that RANTES suppresses HIV-1 replication, as measured by reverse transcriptase activity, in PBM (41.3 +/- 15.2% of control, n = 3, P < 0.05) and AM (30.3 +/- 7.8% of control, n = 3, P < 0.05) in a dose-dependent manner. The other C-C chemokines had no significant effect singly (MIP-1 alpha PBM: 64.8 +/- 21.9%; AM: 115.0 +/- 2.4% of control; MIP-1 beta PBM: 68 +/- 19.6; AM: 63.3 +/- 26.2% of control) but modestly decreased HIV replication when incubated in addition to RANTES (24.5 +/- 6.5% of control). These observations suggest that RANTES plays a key role in modulating HIV-1 replication in mononuclear phagocytes in the blood and lung, and this may have therapeutic implications for prevention and/or treatment of HIV disease.

Cyclosporine inhibits protein kinase C-dependent signals in human peripheral blood lymphocytes

1989 ◽  
Vol 46 (4) ◽  
pp. 292-295 ◽  
Author(s):  
Marvin A. McMillen ◽  
Harold A. Schaefer ◽  
John D. MacArthur ◽  
Thomas A. Adrian ◽  
Irvin M. Modlin
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Blood Lymphocytes ◽  
Human Peripheral Blood Lymphocytes ◽  
Kinase C
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