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Role of PKC-β in chemical allergen-induced CD86 expression and IL-8 release in THP-1 cells

  • Immunotoxicology
  • Published:
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Abstract

We previously demonstrated an age-related decrease in receptor for activated C-kinase (RACK-1) expression and functional deficit in Langerhans cells’ responsiveness. This defect specifically involves the translocation of protein kinase C (PKC)-β. The purpose of this study was to investigate the role of RACK-1 and PKC-β in chemical allergen-induced CD86 expression and IL-8 release in the human promyelocytic cell line THP-1 and primary human dendritic cells (DC). Dinitrochlorobenzene, p-phenylenediamine and diethyl maleate were used as contact allergens. The selective cell-permeable inhibitor of PKC-β and the broad PKC inhibitor GF109203X completely prevented chemical allergen- or lipopolysaccharide (LPS)-induced CD86 expression and significantly modulated IL-8 release (50 % reduction). The selective cell-permeable inhibitor of PKC-ε (also known to bind to RACK-1) failed to modulate allergen- or LPS-induced CD86 expression or allergen-induced IL-8 release, while modulating LPS-induced IL-8 release. The use of a RACK-1 pseudosubstrate, which directly activates PKC-β, resulted in dose-related increase in CD86 expression and IL-8 release. Similar results were obtained with human DC, confirming the relevance of results obtained in THP-1 cells. Overall, our findings demonstrate the role of PKC-β and RACK-1 in allergen-induced CD86 expression and IL-8 production, supporting a central role of PKC-β in the initiation of chemical allergen-induced DC activation.

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Abbreviations

DAG:

Diacylglycerol

DEM:

Diethyl maleate

DNCB:

2, 4-Dinitrochlorobenzene

PPD:

p-Phenylenediamine

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Acknowledgments

This project was supported by Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN2009) titled ‘Glucocorticoid receptor and signal transduction pathways associated with immune cell activation: relevance in autoimmune diseases.’ The authors would like to express their sincere gratitude to Dr Ellaine Ferioli for her careful reading and review of the manuscript.

Conflict of interest

For the past 3 years since the beginning of this work, all authors declare of not having any financial or personal association with any individuals or organizations that could have inappropriately influenced the submitted work.

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Authors and Affiliations

  1. Laboratory of Toxicology, Dipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Università degli Studi di Milano, Via G. Balzaretti 9, 20133, Milan, Italy

    Emanuela Corsini, Valentina Galbiati, Marina Marinovich & Corrado L. Galli

  2. Allergy Research Group, Department of Dermatology and Venereology, University Medical Center Freiburg, Freiburg, Germany

    Philipp R. Esser & Stefan F. Martin

  3. Department of Drug Sciences, Pharmacology, University of Pavia, Pavia, Italy

    Antonella Pinto & Marco Racchi

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  1. Emanuela Corsini
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Correspondence to Emanuela Corsini.

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Corsini, E., Galbiati, V., Esser, P.R. et al. Role of PKC-β in chemical allergen-induced CD86 expression and IL-8 release in THP-1 cells. Arch Toxicol 88, 415–424 (2014). https://doi.org/10.1007/s00204-013-1144-z

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