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The Role of Elongation of Very Long Chain Fatty Acids Family Member 6 (Elovl6) in Allergic Airway Inflammation
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A1294 - The Role of Elongation of Very Long Chain Fatty Acids Family Member 6 (Elovl6) in Allergic Airway Inflammation
Author Block: K. Yoshida, Y. Morishima, H. Sakurai, Y. Tsunoda, M. Nakajima, M. Matsuyama, T. Kiwamoto, Y. Matsuno, I. Yukio, N. Hizawa; University of Tsukuba, Tsukuba, Japan.
Background It is widely accepted that obesity contributes to the onset and severity of asthma; however, its molecular mechanism still remains unclear. A recent study demonstrated that the high intake of palmitic acid (C16:0) increased the number of lung inflammatory cells and exacerbated allergic airway inflammation in an obese mouse model, which suggests that aberrations in fatty acid composition may affect inflammatory responses in asthma. In this study we evaluated the role of elongation of very long chain fatty acids family member 6 (Elovl6), an enzyme that regulates the elongation of C 12-16 saturated and monounsaturated fatty acids, in an experimental mouse model of allergic asthma. Methods Elovl6-deficient (Elovl6-/-) mice of C57BL/6 background were established by specific deletion of the Elovl6 gene segment. Wild-type (WT) C57BL/6 mice and Elovl6-/- mice were sensitized subcutaneously with 100 μg of ovalbumin (OVA) on days 1 and 15, and challenged intranasally with 10 μg of OVA on day 29. Non-immunized mice were sensitized and challenged with normal saline instead of OVA. Forty-eight hours after the last OVA or saline challenge, airway inflammation was assessed by total and differential cell counts in the bronchoalveolar lavage fluid (BALF), lung histology and cytokine levels in the lungs. Results The numbers of inflammatory cells in the BALF were not different between the two genotypes of non-immunized mice. However, compared to WT mice, Elovl6-/- mice showed a significant increase in the total cell, eosinophil and neutrophil counts in the BALF after OVA sensitization/challenge. The histological analysis supported these findings and showed that inflammatory cell infiltration in the peribronchial and perivascular regions was remarkable in the lungs of OVA-immunized Elovl6-/- mice. Mucous goblet cells were also increased in number in the airways, and the mRNA levels of IL-6, IL-13 and IL-17 were upregulated in the lungs of these mice. Conclusion OVA- induced neutrophilic and eosinophilic inflammation and goblet cell hyperplasia in the airways were enhanced under the Elovl6-deficient condition. Our findings indicate that Elovl6-mediated changes in fatty acid composition of airways may have an important role in developing allergic airway inflammation, and that Elovl6 could be a potential therapeutic target for treatment of severe asthma.
Author Block: K. Yoshida, Y. Morishima, H. Sakurai, Y. Tsunoda, M. Nakajima, M. Matsuyama, T. Kiwamoto, Y. Matsuno, I. Yukio, N. Hizawa; University of Tsukuba, Tsukuba, Japan.
Background It is widely accepted that obesity contributes to the onset and severity of asthma; however, its molecular mechanism still remains unclear. A recent study demonstrated that the high intake of palmitic acid (C16:0) increased the number of lung inflammatory cells and exacerbated allergic airway inflammation in an obese mouse model, which suggests that aberrations in fatty acid composition may affect inflammatory responses in asthma. In this study we evaluated the role of elongation of very long chain fatty acids family member 6 (Elovl6), an enzyme that regulates the elongation of C 12-16 saturated and monounsaturated fatty acids, in an experimental mouse model of allergic asthma. Methods Elovl6-deficient (Elovl6-/-) mice of C57BL/6 background were established by specific deletion of the Elovl6 gene segment. Wild-type (WT) C57BL/6 mice and Elovl6-/- mice were sensitized subcutaneously with 100 μg of ovalbumin (OVA) on days 1 and 15, and challenged intranasally with 10 μg of OVA on day 29. Non-immunized mice were sensitized and challenged with normal saline instead of OVA. Forty-eight hours after the last OVA or saline challenge, airway inflammation was assessed by total and differential cell counts in the bronchoalveolar lavage fluid (BALF), lung histology and cytokine levels in the lungs. Results The numbers of inflammatory cells in the BALF were not different between the two genotypes of non-immunized mice. However, compared to WT mice, Elovl6-/- mice showed a significant increase in the total cell, eosinophil and neutrophil counts in the BALF after OVA sensitization/challenge. The histological analysis supported these findings and showed that inflammatory cell infiltration in the peribronchial and perivascular regions was remarkable in the lungs of OVA-immunized Elovl6-/- mice. Mucous goblet cells were also increased in number in the airways, and the mRNA levels of IL-6, IL-13 and IL-17 were upregulated in the lungs of these mice. Conclusion OVA- induced neutrophilic and eosinophilic inflammation and goblet cell hyperplasia in the airways were enhanced under the Elovl6-deficient condition. Our findings indicate that Elovl6-mediated changes in fatty acid composition of airways may have an important role in developing allergic airway inflammation, and that Elovl6 could be a potential therapeutic target for treatment of severe asthma.
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