| First Author | Nagano T | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 9 | Pages | e108373 |
| PubMed ID | 25269075 | Mgi Jnum | J:222461 |
| Mgi Id | MGI:5644635 | Doi | 10.1371/journal.pone.0108373 |
| Citation | Nagano T, et al. (2014) Phospholipase cepsilon, an effector of ras and rap small GTPases, is required for airway inflammatory response in a mouse model of bronchial asthma. PLoS One 9(9):e108373 |
| abstractText | BACKGROUND: Phospholipase Cepsilon (PLCepsilon) is an effector of Ras and Rap small GTPases and expressed in non-immune cells. It is well established that PLCepsilon plays an important role in skin inflammation, such as that elicited by phorbol ester painting or ultraviolet irradiation and contact dermatitis that is mediated by T helper (Th) 1 cells, through upregulating inflammatory cytokine production by keratinocytes and dermal fibroblasts. However, little is known about whether PLCepsilon is involved in regulation of inflammation in the respiratory system, such as Th2-cells-mediated allergic asthma. METHODS: We prepared a mouse model of allergic asthma using PLCepsilon+/+ mice and PLCepsilonDeltaX/DeltaX mutant mice in which PLCepsilon was catalytically-inactive. Mice with different PLCepsilon genotypes were immunized with ovalbumin (OVA) followed by the challenge with an OVA-containing aerosol to induce asthmatic response, which was assessed by analyzing airway hyper-responsiveness, bronchoalveolar lavage fluids, inflammatory cytokine levels, and OVA-specific immunoglobulin (Ig) levels. Effects of PLCepsilon genotype on cytokine production were also examined with primary-cultured bronchial epithelial cells. RESULTS: After OVA challenge, the OVA-immunized PLCepsilonDeltaX/DeltaX mice exhibited substantially attenuated airway hyper-responsiveness and broncial inflammation, which were accompanied by reduced Th2 cytokine content in the bronchoalveolar lavage fluids. In contrast, the serum levels of OVA-specific IgGs and IgE were not affected by the PLCepsilon genotype, suggesting that sensitization was PLCepsilon-independent. In the challenged mice, PLCepsilon deficiency reduced proinflammatory cytokine production in the bronchial epithelial cells. Primary-cultured bronchial epithelial cells prepared from PLCepsilonDeltaX/DeltaX mice showed attenuated pro-inflammatory cytokine production when stimulated with tumor necrosis factor-alpha, suggesting that reduced cytokine production in PLCepsilonDeltaX/DeltaX mice was due to cell-autonomous effect of PLCepsilon deficiency. CONCLUSIONS: PLCepsilon plays an important role in the pathogenesis of bronchial asthma through upregulating inflammatory cytokine production by the bronchial epithelial cells. |
