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Sex‐based differences in 15‐lipoxygenase and airway reactivity
Author(s) -
Pfister Sandra L,
Pillay Thivashnee
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.806.5
Sex‐based differences are important in the incidence, severity and progression of asthma. Our laboratory studies the role of lipid mediators derived from the 15‐lipoxygenase (LO) pathway of arachidonic acid (AA) metabolism and showed previously that this pathway is regulated in a sex‐specific manner in the pulmonary vasculature. The goal of the present study was to determine if similar changes occur in the airway smooth muscle of young prepubescent male and female rabbits. Bronchioles were incubated with 14C‐AA, and the extracted metabolites resolved by RP‐HPLC. The production of 15‐HETE was enhanced in males (40.2 cpm/mg vs 8.7 cpm/mg; male vs female). Western analysis showed that 15‐LO protein expression was 10‐fold greater in males (relative intensity 15‐LO/β‐actin; 13 ± 5 vs 1 ± 0.2; male vs female). Additional studies examined airway reactivity in isolated bronchioles. In males the average response to KCl (120 mM) was 0.4 ± 0.04 grams. Female bronchioles had little to no contractile response to KCl (0.05 ± 0.01 grams). In males, methacholine‐induced a concentration dependent contraction of bronchioles that was partially blocked by the LO inhibitor, NDGA (maximal response; 124 ± 9 % vs 83 ± 12%; control vs NDGA). In conclusion, increased 15‐LO expression and activity in male airways may explain the increased incidence of asthma observed in boys before puberty. Supported by NIH HL‐093181.