Volume 120, Issue 1 , Pages 200-206, July 2007
Protein kinase Cζ: A novel protective neonatal T-cell marker that can be upregulated by allergy prevention strategies
Background
Variations in neonatal T-cell function have been associated with allergic disease.
Objectives
To examine the relationship between neonatal T-cell protein kinase (PKC) expression and subsequent allergic disease.
Methods
T cells were purified from cord blood samples (n = 74) obtained from a cohort of mothers who received either 4 g/d fish oil or a placebo from 20 weeks of gestation. PKC expression was examined in relationship to supplementation, fatty acid levels, cytokine production, and allergic outcomes at 1 year and 2.5 years of age.
Results
Neonatal T-cell PKCζ expression was lower in children who had evidence of allergic disease at 1 year (P = .001) and 2.5 years (P = .052) of age. It was also lower in children with sensitization (positive skin prick test) at each age (P = .02 and P = .072, respectively). PKCζ expression was inversely correlated to PKCα (r = −0.28; P = .025), which was strongly related to IL-5 responses to allergens (ovalbumin, r = 0.59; P = .003; dust mite, r = 0.52; P = .011) at 1 year of age. Fish oil supplementation was associated with significantly higher PKCζ expression (P = .014), whereas most other isozymes were reduced by fish oil supplementation.
Conclusion
This is the first study to show that allergic disease is associated with altered expression of T-cell PKC isozymes in the neonatal period. It has also demonstrated that fish oil can modulate expression of PKC isozymes in a potentially favorable direction.
Clinical implications
Protein kinase Cζ should be explored further as an early marker and potential target for disease prevention.
Key words: Protein kinase C, neonate, cytokines, fish oil, polyunsaturated fatty acids, atopic dermatitis, sensitization, allergy prevention, predictive markers, cord blood, allergy
Abbreviations used: DHA, Docosahexaenoic acid, EPA, Eicosapentaenoic acid, MC, Mononuclear cell, ω-3 LCPUFA, ω-3 Long chain polyunsaturated fatty acid, OR, Odds ratio, PKC, Protein kinase C, SEB, Staphylococcus aureus enterotoxin B, SPT, Skin prick test
Supported by the National Health and Medical Research Council of Australia. J.A.D. is supported by the Child Health Research Foundation of Western Australia.Disclosure of potential conflict of interest: The authors have received grant support from the National Health and Medical Research Council of Australia.
PII: S0091-6749(07)00644-6
doi:10.1016/j.jaci.2007.03.045
© 2007 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Volume 120, Issue 1 , Pages 200-206, July 2007
