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Involvement of protein kinase C in competence induction of macrophages to generate T suppressor cells.
J Immunol. 1991 Jun 15; 146(12):4085-91.JI

Abstract

We have previously described an Ia-expressing macrophage hybridoma clone, termed clone 59, which attains the ability to induce Ts cells after activation with murine rIFN-gamma. In this report, we show that a protein kinase C (PKC) activator, PMA (10 ng/ml) can replace IFN-gamma in inducing this form of macrophage competence. IFN-gamma-induced cellular competence was abrogated specifically by a PKC inhibitor but not by inhibitors that have specificity for cyclic nucleotide-dependent protein kinases. Furthermore, PGE2 known to induce protein kinase A in murine macrophages also failed to induce competence. In contrast, the ability to induce Th responses was neither dependent on IFN-gamma nor inhibited by prior treatment with protein kinase inhibitors. Furthermore, PKC depletion of macrophages by treatment with high doses (100 ng/ml) of PMA abrogated their ability to induce Ts cells. In addition, PKC-depleted macrophages failed to regain the ability to stimulate Ts cells after further treatment with IFN-gamma. The ability of IFN-gamma to modulate macrophage-mediated induction of Ts cells does not clearly correlate with an increased Ia expression as inducible expression of Ia was not consistently abrogated by PKC inhibitor treatment. In addition, PKC inhibitors failed to prevent the production of the cytokines IL-1 and IL-6. However, incubation of IFN-gamma or PMA-treated macrophages with antibodies recognizing the putative IJ ligand blocked the ability to induce Ts cells, suggesting the expression of these determinants on accessory cells is responsible for Ts induction.

Authors+Show Affiliations

Department of Pathology, Harvard Medical School, Boston, MA 02115.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1710237

Citation

Jayaraman, S, et al. "Involvement of Protein Kinase C in Competence Induction of Macrophages to Generate T Suppressor Cells." Journal of Immunology (Baltimore, Md. : 1950), vol. 146, no. 12, 1991, pp. 4085-91.
Jayaraman S, Mensi N, Webb DR, et al. Involvement of protein kinase C in competence induction of macrophages to generate T suppressor cells. J Immunol. 1991;146(12):4085-91.
Jayaraman, S., Mensi, N., Webb, D. R., & Dorf, M. E. (1991). Involvement of protein kinase C in competence induction of macrophages to generate T suppressor cells. Journal of Immunology (Baltimore, Md. : 1950), 146(12), 4085-91.
Jayaraman S, et al. Involvement of Protein Kinase C in Competence Induction of Macrophages to Generate T Suppressor Cells. J Immunol. 1991 Jun 15;146(12):4085-91. PubMed PMID: 1710237.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of protein kinase C in competence induction of macrophages to generate T suppressor cells. AU - Jayaraman,S, AU - Mensi,N, AU - Webb,D R, AU - Dorf,M E, PY - 1991/6/15/pubmed PY - 1991/6/15/medline PY - 1991/6/15/entrez SP - 4085 EP - 91 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 146 IS - 12 N2 - We have previously described an Ia-expressing macrophage hybridoma clone, termed clone 59, which attains the ability to induce Ts cells after activation with murine rIFN-gamma. In this report, we show that a protein kinase C (PKC) activator, PMA (10 ng/ml) can replace IFN-gamma in inducing this form of macrophage competence. IFN-gamma-induced cellular competence was abrogated specifically by a PKC inhibitor but not by inhibitors that have specificity for cyclic nucleotide-dependent protein kinases. Furthermore, PGE2 known to induce protein kinase A in murine macrophages also failed to induce competence. In contrast, the ability to induce Th responses was neither dependent on IFN-gamma nor inhibited by prior treatment with protein kinase inhibitors. Furthermore, PKC depletion of macrophages by treatment with high doses (100 ng/ml) of PMA abrogated their ability to induce Ts cells. In addition, PKC-depleted macrophages failed to regain the ability to stimulate Ts cells after further treatment with IFN-gamma. The ability of IFN-gamma to modulate macrophage-mediated induction of Ts cells does not clearly correlate with an increased Ia expression as inducible expression of Ia was not consistently abrogated by PKC inhibitor treatment. In addition, PKC inhibitors failed to prevent the production of the cytokines IL-1 and IL-6. However, incubation of IFN-gamma or PMA-treated macrophages with antibodies recognizing the putative IJ ligand blocked the ability to induce Ts cells, suggesting the expression of these determinants on accessory cells is responsible for Ts induction. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/1710237/Involvement_of_protein_kinase_C_in_competence_induction_of_macrophages_to_generate_T_suppressor_cells_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=1710237 DB - PRIME DP - Unbound Medicine ER -