St-Denis, Anik; Chano, Frédéric; Tremblay, Pierre; St-Pierre, Yves 
ORCID: https://orcid.org/0000-0002-1948-2041 et Descoteaux, Albert ORCID: https://orcid.org/0000-0002-0633-5309
(1998).
Protein kinase C-alpha modulates lipopolysaccharide-induced functions in a murine macrophage cell line
Journal of Biological Chemistry
, vol. 273
, nº 49.
pp. 32787-32792.
DOI: 10.1074/jbc.273.49.32787.
Résumé
Lipopolysaccharide (LPS), a potent modulator of macrophage functional activity, binds to CD14 and triggers the activation of several protein kinases, leading to the secretion of variety of immunomodulatory molecules such as nitric oxide and proinflammatory cytokines. In this study, we have examined the role of the alpha isoenzyme of protein kinase C (PKC) in the regulation of LPS-initiated signal transduction in macrophages. To this end, we have stably overexpressed a dominant-negative (DN) version of PKC-alpha (DN PKC-alpha) in the murine macrophage cell line RAW 264.7. Clones overexpressing DN PKC-alpha were indistinguishable from the parental line with respect to morphology and growth characteristics. At the functional level, DN PKC-alpha overexpression strongly inhibited LPS-induced interleukin-la mRNA accumulation, and to a lesser extent inducible nitric oxide synthase and tumor necrosis factor-alpha expression. DN-PKC-alpha overexpression did not cause a general unresponsiveness to LPS, as secretion of the matrix metalloproteinase-9 was up-regulated in our DN PKC-alpha-overexpressing clones. Moreover, LPS-induced phosphorylation and degradation of I kappa B alpha, NF-kappa B activation, as well as p38 mitogen-activated protein kinase and Jun N-terminal kinase phosphorylation, were not affected by DN PKC-alpha overexpression. Collectively, these data provide evidence that PKC-alpha regulates selective LPS-induced macrophage functions involved in host defense and inflammation.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 07 juill. 2025 18:46 |
| Dernière modification: | 07 juill. 2025 18:46 |
| URI: | https://espace.inrs.ca/id/eprint/15179 |
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