Protein kinase Cζ: A novel protective neonatal T-cell marker that can be upregulated by allergy prevention strategies
Received 15 December 2006; received in revised form 9 March 2007; accepted 13 March 2007. published online 04 June 2007.
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.
aFrom the School of Pediatrics and Child Health, University of Western Australia, Perth
bDepartment of Immunopathology, Women and Children's Hospital, Adelaide, and the Department of Pediatrics, University of Adelaide, Australia
Reprint requests: Susan L. Prescott, MBBS, PhD, FRACP, School of Pediatrics and Child Health, University of Western Australia, PO Box D184, Princess Margaret Hospital, Perth WA 6001, Australia.
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.
ABSTRACT