Methods: Allergic airway inflammation was induced in wild type C57Bl and 12/15-LOX knockout (12/15-KO) mice by sensitization and exposure to Dp. Lung samples were obtained 24 hours after: 1. a single nebulization (SN, n=8), or 2. a series of repeated nebulizations performed once daily for 3 weeks (RN, n=8). Sham challenged mice were used as controls. Expression of 84 genes was evaluated using SYBR Green-based microarray. The expression of the selected genes was verified using TaqMan-based real-time PCR.
Results: After SN in C57Bl mice significant (>2-fold) up-regulation of Ccl17, Clca3, Csf3r, Ear11, Il17a, Il9 and Retnlg expression was demonstrated. After RN significant up-regulation of expression of 44 genes was found in C57Bl mice. The strongest up-regulation (>10-fold) was demonstrated for Arg1, Ccl26, Clca3, Ear11, Il13ra2, Il17a, Il21, Il25, Il3, Il9 and Prg2. In 12/15-KO mice attenuated up-regulation of those gene expression was found after RN, except for Clca3, which expression was significantly greater than in C57Bl mice. After SN greater expression of Arg1, Ccl24, Ccl26, Clca3, Mmp9, Prg2, and Retnlg was found in 12/15-KO in comparison with C57Bl mice.
Conclusions: 12/15-LOX modulates expression of several genes during Dp-induced allergic airway inflammation. The products of 12/15-LOX pathway may be directly involved in inhibition of Clca3 expression during allergen-induced airway inflammation.