We have previously shown that in rats, sPLA2 and cPLA2 play opposing roles in the pathophysiology of ovalbumin (OVA)-induced experimental allergic bronchitis (OVA-EAB), an asthma model: Upon disease induction sPLA2 expression and production of the broncho-constricting CysLTs are elevated, whereas cPLA2 expression and the broncho-dilating PGE2 production are suppressed.
In vitro responses of asthma (N=26) and healthy (N=11) subject PBMC samples to allergen stimulation in the presence and absence of cPLA(2)alpha inhibition or 5-lipoxygenase inhibition were compared at the gene expression level using oligonucleotide arrays and at the protein level using ELISA.
We analysed the cPLA(2) promoter regions containing (CA)(n) and (T)(n) repeats in 87 patients with severe asthma and in 48 control subjects by bidirectional sequencing.
This study demonstrates, for the first time in vivo, a negative feedback between sPLA2 and cPLA2 and assigns opposing roles for these enzymes in asthma pathophysiology: sPLA2 activation induces production of the bronchoconstrictor CysLT and suppresses cPLA2 expression and the subsequent production of the bronchodilator PGE2.