Protein kinase C isozymes as potential therapeutic targets in immune disorders

Abstract

Background: Members of the protein kinase C (PKC) family are key signalling mediators in immune responses, and pharmacological inhibition of PKCs may be useful for treating immune-mediated diseases. Objective: To review and discuss the insights gained so far into various PKC isozymes and the therapeutic potential and challenges of developing PKC inhibitors for immune disorder therapy. Methods: A literature review of the role of PKCs in immune cell signalling and recent studies describing immune functions associated with PKC isozyme deficiency in relevant mouse disease models, followed by specific case studies of current and potential therapeutic strategies targeting PKCs. Results/conclusion: There is vast amount of data supporting PKC isozymes as attractive drug targets for certain immune disorders. Although the development of specific PKC isozyme inhibitors has been challenging, some progress has been made. It remains to be seen if broad-scale or isozyme-selective inhibition of PKC will have clinical efficacy.

Keywords::

• asthma
• inflammation
• inflammatory bowel disease (IBD)
• kinase inhibitor
• protein kinase C (PKC)
• rheumatoid arthritis (RA)
• systemic lupus erythematosus (SLE)

Acknowledgements

The authors apologize for not being able to cite original work of many colleagues due to space restraints. We thank Min Wong and Chris Gabel for helpful suggestions and critical comments on the manuscript.