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Njau F, Haller H. Calcium Dobesilate Modulates PKCδ-NADPH Oxidase- MAPK-NF-κB Signaling Pathway to Reduce . Antioxidants (Basel). 2021;10(11)doi: 10.3390/antiox10111798.
Njau, F., & Haller, H. (2021). Calcium Dobesilate Modulates PKCδ-NADPH Oxidase- MAPK-NF-κB Signaling Pathway to Reduce . Antioxidants (Basel, Switzerland), 10(11), . https://doi.org/10.3390/antiox10111798
Njau, Florence, and Haller, Hermann. "Calcium Dobesilate Modulates PKCδ-NADPH Oxidase- MAPK-NF-κB Signaling Pathway to Reduce ." Antioxidants (Basel, Switzerland) vol. 10,11 (2021). doi: https://doi.org/10.3390/antiox10111798
Njau F, Haller H. Calcium Dobesilate Modulates PKCδ-NADPH Oxidase- MAPK-NF-κB Signaling Pathway to Reduce . Antioxidants (Basel). 2021 Nov 11;10(11). doi: 10.3390/antiox10111798. PMID: 34829669; PMCID: PMC8615002.
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Antioxidants (Basel). 2021 Nov 11;10(11). doi: 10.3390/antiox10111798.

Calcium Dobesilate Modulates PKCδ-NADPH Oxidase- MAPK-NF-κB Signaling Pathway to Reduce .

Antioxidants (Basel, Switzerland)

Florence Njau, Hermann Haller

Affiliations

  1. Division of Nephrology, Hannover Medical School, 30625 Hannover, Germany.

PMID: 34829669 PMCID: PMC8615002 DOI: 10.3390/antiox10111798

Abstract

Monocyte-to-macrophage differentiation results in the secretion of various inflammatory mediators and oxidative stress molecules necessary for atherosclerosis pathogenesis. Consequently, this differentiation represents a potential clinical target in atherosclerosis. Calcium dobesilate (CaD), an established vasoactive and angioprotective drug in experimental models of diabetic microvascular complications reduces oxidative stress and inhibits inflammation via diverse molecular targets; however, its effect on monocytes/macrophages is poorly understood. In this study, we investigated the anti-inflammatory mechanism of CaD during phorbol 12-myristate 13-acetate (PMA)-induced monocyte-to-macrophage differentiation in in vitro models of sepsis (LPS) and hyperglycemia, using THP-1 monocytic cell line. CaD significantly suppressed CD14, TLR4, and MMP9 expression and activity, lowering pro-inflammatory mediators, such as IL1β, TNFα, and MCP-1. The effects of CaD translated through to studies on primary human macrophages. CaD inhibited reactive oxygen species (ROS) generation, PKCδ, MAPK (ERK1/2 and p38) phosphorylation, NOX2/p47phox expression, and membrane translocation. We used hydrogen peroxide (H2O2) to mimic oxidative stress, demonstrating that CaD suppressed PKCδ activation via its ROS-scavenging properties. Taken together, we demonstrate for the first time that CaD suppresses CD14, TLR4, MMP9, and signature pro-inflammatory cytokines, in human macrophages, via the downregulation of PKCδ/NADPH oxidase/ROS/MAPK/NF-κB-dependent signaling pathways. Our data present novel mechanisms of how CaD alleviates metabolic and infectious inflammation.

Keywords: PKCδ; atherosclerosis; calcium dobesilate; inflammation; monocyte-macrophage differentiation; oxidative stress

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