The mechanism of development and exacerbation of virus-induced asthma analyzed by a lipid mediator gene knock-out mice

• Project/Area Number: 20591267
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Gunma Institute of Public Health and Environmental Sciences
• Principal Investigator: KATO Masahiko Gunma Institute of Public Health and Environmental Sciences, 研究企画係, 研究員 (30292593)
• Co-Investigator(Kenkyū-buntansha): YAMADA Yoshiyuki 群馬県衛生環境研究所, 研究企画係, 研究員 (80309252) ; HAYASHI Yasuhide 群馬県衛生環境研究所, 研究企画係, 研究員 (30238133)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 小児免疫 / アレルギー / 膠原病学 / 気管支喘息 / ウイルス感染 / 好酸球 / 脂質メディエーター / 遺伝子

Research Abstract

To clarify the pathogenesis of exacerbations of asthma due to viral infection, we examined bronchial resistance, peripheral blood and bronchial alveolar fluid (BALF) analyses and multiple types of cytokines/chemokines using an experimental asthma model mice infected with respiratory syncytial virus (RSV). The levels of BALF and tissue eosinophils showed significant increase in ovalbumin (OVA) and OVA/RSV groups compared with controls. MIP-1αin BALF was significantly increased in OVA/RSV groups compared with RSV groups, OVA groups, and control groups. Serum IL-5 in OVA groups and serum IL-17 in OVA/RSV groups were also higher than in controls. These findings suggest that eosinophilic inflammation via MIP-1α may play an important role in acute exacerbations of asthma model induced by RSV.

Research Products

• [Journal Article] Prominent eosinophilia but less eosinophil activation in a patient with Omenn syndrome. (2010)
  • Author(s): Seki M, Kimura H, Mori A, Shimada A, Yamada Y, Maruyama K, Hayashi Y, Agematsu K, Morio T, Yachie A, Kato M
  • Journal Title: Pediatr Int 52
  • Peer Reviewed
• [Journal Article] Different cytokine profile and eosinophil activation are involved in rhinovirus- and RS virus-induced acute exacerbation of childhood wheezing. (2010)
  • Author(s): Kato M, Tsukagoshi H, Yoshizumi M, Saitoh M, Kozawa K, Yamada Y, Maruyama K, Hayashi Y, Kimura H
  • Journal Title: Pediatr Allergy Immunol 22
  • Peer Reviewed
• [Journal Article] Serum eosinophil cationic protein and 27 cytokines/chemokines production in acute exacerbation of childhood asthma. (2010)
  • Author(s): Kato M, Yamada Y, Maruyama K, Hayashi Y
  • Journal Title: Int Arch Allergy Immunol 152(Suppl 1) Pages: 62-66
  • Peer Reviewed
• [Journal Article] Effects of respiratory syncytial virus infection and major basic protein derived from eosinophils in pulmonary alveolar epithelial cells (A549). (2010)
  • Author(s): Ishioka T, Kimura H, Kita H, Obuchi M, Hoshino H, Noda M, Nishina A, Kozawa K, Kato M
  • Journal Title: Cell Biol Int (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] 小児気管支喘息発作時の原因ウイルスとサイトカイン/ケモカイン産生および好酸球の活性化 (2010)
  • Author(s): 加藤政彦
  • Journal Title: 日本小児呼吸器疾患学会誌 21 Pages: 134-142
  • Peer Reviewed
• [Journal Article] Different cytokine profile and eosinophil activation are involved in rhinovirus-and RS virus-induced acute exacerbation of childhood wheezing. (2010)
  • Author(s): Kato M, Tsukagoshi H, Yoshizumi M, Saitoh M, Kozawa K, Yamada Y, Maruyama K, Hayashi Y, Kimura H.
  • Journal Title: Pediatr Allergy Immunol Volume: Feb22
  • Peer Reviewed
• [Journal Article] Serum eosinophil cationic protein and 27 cytokines/chemokines production in acute exacerbation of childhood asthma. (2010)
  • Author(s): Kato M, Yamada Y, Maruyama K, Hayashi Y.
  • Journal Title: Int Arch Allergy Immunol Volume: 152 Pages: 62-66
  • Peer Reviewed
• [Journal Article] Prominent eosinophilia but less eosinophil activation in a patient with Omenn syndrome. (2010)
  • Author(s): Seki M, Kimura H, Mori A, Shimada A, Yamada Y, Maruyama K, Hayashi Y, Agematsu K, Morio T, Yachie A, Kato M.
  • Journal Title: Pediatr Int Volume: 52
  • Peer Reviewed
• [Journal Article] Relationships between cellular events and signaling pathways in various pesticide-affected neural cells : Mini Review. (2010)
  • Author(s): Kimura H, Tsukagoshi H, Aoyama Y, Nishina A, Yamaguchi T, Iijima A, Kato M, Kozawa K.
  • Journal Title: Toxin Rev Volume: 29 Pages: 43-50
  • Peer Reviewed
• [Journal Article] Effects of respiratory syncytial virus infection and major basic protein derived from eosinophils in pulmonary alveolar epithelial cells(A549). (2010)
  • Author(s): Ishioka T, Kimura H, Kita H, Obuchi M, Hoshino H, Noda M, Nishina A, Kozawa K, Kato M.
  • Journal Title: Cell Biol Int Volume: Oct27(Epub)
  • Peer Reviewed
• [Journal Article] 救急外来における気管支喘息患者の実態と吸入ステロイド薬処方の影響-他施設コホート観察研究- (2010)
  • Author(s): 蝶名林直彦, 杉山公美弥, 加藤政彦, 木村輝明, 望月博之, 安場広高, 吉原重美, 福田健, 森川昭廣, 足立満
  • Journal Title: アレルギー Volume: 59 Pages: 123-136
  • Peer Reviewed
• [Journal Article] 小児気管支喘息発作時の原因ウイルスとサイトカイン/ケモカイン産生および好酸球の活性化 (2010)
  • Author(s): 加藤政彦
  • Journal Title: 日本小児呼吸器疾患学会誌 Volume: 21 Pages: 134-142
  • Peer Reviewed
• [Journal Article] 小児科医のノートから.RSウイルス感染症の最近の動向-勤務医の視点から (2010)
  • Author(s): 加藤政彦
  • Journal Title: 群馬県小児科医会便り Volume: 53 Pages: 33-34
• [Journal Article] Peripheral lymphocyte subset and serum cytokine profiles of patients with West syndrome. (2009)
  • Author(s): Shiihara T, Miyashita M, Yoshizumi M, Watanabe M, Yamada Y, Kato M.
  • Journal Title: Brain Dev Nov 30(Epub)
  • NAID: 10027492486
  • Peer Reviewed
• [Journal Article] アレルギー疾患.診断.血液検査 (2009)
  • Author(s): 加藤政彦
  • Journal Title: 日本臨牀 67 Pages: 2100-2104
• [Journal Article] 平成20年度感染症流行予測調査結果 (2009)
  • Author(s): 長井綾子, 鈴木智之, 塩原正枝, 森田幸雄, 加藤政彦
  • Journal Title: 群馬県衛生環境研究所年報(1340―265X) 40 Pages: 70-73
• [Journal Article] Interferon-γ enhances human eosinophil effector functions induced by granulocyte-macrophage colony-stimulating factor or interleukin-5. (2008)
  • Author(s): Yamaguchi T, Kimura H, Kurabayashi M, Kozawa K, Kato M
  • Journal Title: Immunol Lett. 118 Pages: 88-95
  • Peer Reviewed
• [Journal Article] Serum cytokines/chemokines profiles in neonates with meconium aspiration syndrome. (2008)
  • Author(s): Okazaki K, Kondo M, Kato M, Kakinuma R, Nishida A, Noda M, Taniguchi K, Kimura H
  • Journal Title: Pediatrics. 121
  • Peer Reviewed
• [Journal Article] Release of cytokines/chemokines and cell death in UVB-irradiated human keratinocytes, HaCaT. (2008)
  • Author(s): Yoshizumi M, Nakamura T, Kato M, Ishioka T, Kozawa K, Wakamatsu K, Kimura H
  • Journal Title: Cell Biol Int. 32 Pages: 1405-1411
  • Peer Reviewed
• [Journal Article] FIP1L1/PDGFR alpha synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome. (2008)
  • Author(s): Yamada Y, Sanchez-Aguilera A, Brandt EB, McBride M, Al-Moamen NJ, Finkelman FD, Williams DA, Cancelas JA, Rothenberg ME
  • Journal Title: Blood. 112 Pages: 2500-2507
  • Peer Reviewed
• [Journal Article] An imported dengue fever case by dengue virus 3 (DENV-3) infection in Gunma, Japan (2008)
  • Author(s): Morita Y, Kogure H, Sandoh M, Kawashima G, Sato Y, Nanba S, Shoda Y, Suzuki T, Shiono M, Shiobara M, Kato M, Kozawa K, Noda M, Okabe N, Kimura H.
  • Journal Title: Jpn J Infect Dis 61 Pages: 90-92
  • Peer Reviewed
• [Journal Article] Elevation of High-Mobility Group Box 1 Concentration in Asphyxiated Neonates (2008)
  • Author(s): Okazaki K, Kondo M, Kato M, Kakinuma R, Nishida A, Noda M, Kimura H.
  • Journal Title: Neonatology 94 Pages: 105-109
  • Peer Reviewed
• [Journal Article] Serum cytokines/chemokines profiles in neonates with meconium aspiration syndrome (2008)
  • Author(s): Okazaki K, Kondo M, Kato M, Kakinuma R, Nishida A, Noda M, Taniguchi K, Kimura H.
  • Journal Title: Pediatrics 121
  • Peer Reviewed
• [Journal Article] Interferon-γ enhances human eosinophil effector functions induced by granulocyte-macrophage colony-stimulating factor orinterleukin-5 (2008)
  • Author(s): Yamaguchi T, Kimura H, Kurabayashi M, Kozawa K, Kato M.
  • Journal Title: Immunol Lett 118 Pages: 88-95
  • Peer Reviewed
• [Journal Article] Differential diagnosis of primary versus metastatic pulmonary adenocarcinomas using gene mutation analyses : a case report (2008)
  • Author(s): Nakazato Y, Tanaka R, Seki E, Iijima M, Kojima M, Yoshizumi M, Kato M, Kimura H, Kozawa K, Goya T.
  • Journal Title: J Thorac Oncol 3 Pages: 931-934
  • Peer Reviewed
• [Journal Article] Discovery of mitocryptide-1, a neutrophil-activating cryptide from healthy porcine heart (2008)
  • Author(s): Mukai H, Hokari Y, Seki T, Takao T, Kubota M, Matsuo Y, Tsukagoshi H, Kato M, Kimura H, Shimonishi Y, Kiso Y, Nishi Y, Wakamatsu K, Munekata E.
  • Journal Title: J Biol Chem 283 Pages: 30596-30605
  • Peer Reviewed
• [Journal Article] Release of cytokines/chemokines and cell death in UVB-irradiated human keratinocytes, HaCaT (2008)
  • Author(s): Yoshizumi M, Nakamura T, Kato M, Ishioka T, Kozawa K, Wakamatsu K, Kimura H.
  • Journal Title: Cell Biol Int 32 Pages: 1405-1411
  • Peer Reviewed
• [Journal Article] Temporal alterations in concentrations of sera cytokines/chemokines in sepsis due to group B streptococcus infection in a neonate (2008)
  • Author(s): Okazaki K, Kondo M, Kato M, Nishida A, Takahashi H, Noda M, Kimura H.
  • Journal Title: Jpn J Infect Dis 61 Pages: 382-385
  • NAID: 40016249988
  • Peer Reviewed
• [Journal Article] Hemophagocytic lymphohistiocytosis associated with uncontrolled inflammatory cytokinemia and cytokinemia was caused by systemic anaplastic large cell lymphoma : a case report and review of the literature (2008)
  • Author(s): Shimada A, Kato M, Tamura K, Hirato J, Kanegane H, Takechi Y, Park M, Sotomatsu M, Hatakeyama S, Hayashi Y.
  • Journal Title: J Pediatr Hematol Oncol 30 Pages: 785-787
  • Peer Reviewed
• [Journal Article] ウイルス感染と酸化ストレス (2008)
  • Author(s): 加藤政彦
  • Journal Title: アレルギー・免疫 15 Pages: 1050-1058
• [Journal Article] Differential effects of corticosteroids on serum eosinophil cationic protein and cytokine production in rhinovirus- and RS virus-induced acute exacerbation of childhood asthma.
  • Author(s): Kato M, Yamada Y, Maruyama K, Hayashi Y
  • Journal Title: Int Arch Allergy Immunol (in press)
  • Peer Reviewed
• [Presentation] Differential effects of systemic corticosteroids on serum eosinophil cationic protein and cytokine profile in rhinovirus- and RS virus-induced acute exacerbation of childhood asthma. (2011)
  • Author(s): Kato M, Yamada Y, Maruyama K, Hayashi Y
  • Organizer: 67th Annual meeting of American Allergy, Asthma and Immunology.
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-03-19
• [Presentation] Differential effects of systemic corticosteroids on serum eosinophil cationic protein and cytokine profile in rhinovirus- and RS virus-induced acute exacerbation of childhood asthma. (2011)
  • Author(s): Kato M, Yamada Y, Maruyama K, Hayashi Y.
  • Organizer: 67th Annual meeting of American Allergy, Asthma and Immunology
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-03-19
• [Presentation] 後方視的検討で発見された小児好酸球性食道炎 (2010)
  • Author(s): 山田佳之, 加藤政彦
  • Organizer: 第47回日本小児アレルギー学会
  • Place of Presentation: 横浜市
  • Year and Date: 2010-12-05
• [Presentation] ライノウイルスおよびRSウイルスによる小児気管支喘息発作時の血清中サイトカイン/ケモカイン産生と好酸球活性化の相違 (2010)
  • Author(s): 加藤政彦, 山田佳之
  • Organizer: 第47回日本小児アレルギー学会
  • Place of Presentation: 横浜市
  • Year and Date: 2010-12-04
• [Presentation] 小児消化管アレルギー小児での食道好酸球浸潤に関する後方視的検討 小児好酸球性食道炎患者は存在したか (2010)
  • Author(s): 山田佳之, 加藤政彦
  • Organizer: 第60回日本アレルギー学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2010-11-26
• [Presentation] ライノおよびRSウイルスによる小児気管支喘息発作時の血清中サイトカイン産生と好酸球活性化の相違について (2010)
  • Author(s): 加藤政彦,山田佳之
  • Organizer: 第60回日本アレルギー学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2010-11-25
• [Presentation] 小児喘息と気道感染ライノおよびRSウイルスによる小児気管支喘息発作時の血清中サイトカイン産生と好酸球活性化の相違について (2010)
  • Author(s): 加藤政彦, 山田佳之
  • Organizer: 第60回日本アレルギー学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2010-11-25
• [Presentation] ライノウイルスとRSウイルスによる小児気管支喘息発作時の血清中サイトカイン/ケモカイン産生の相違と治療の影響について (2010)
  • Author(s): 加藤政彦, 山田佳之, 丸山健一, 林泰秀
  • Organizer: 第24回アレルギー・好酸球研究会(2010)
  • Place of Presentation: 東京
  • Year and Date: 2010-06-19
• [Presentation] 好酸球性胃腸疾患の4例 (2010)
  • Author(s): 山田佳之, 西明, 江原佳史, 加藤政彦, 林泰秀
  • Organizer: 第24回アレルギー・好酸球研究会(2010)
  • Place of Presentation: 東京
  • Year and Date: 2010-06-19
• [Presentation] 当科にて経験した血球貪食症候群12例の臨床的検討 (2010)
  • Author(s): 外松学, 佐野弘純, 朴明子, 山田佳之, 加藤政彦, 林泰秀
  • Organizer: 第113回日本小児科学会学術集会
  • Place of Presentation: 盛岡市
  • Year and Date: 2010-04-24
• [Presentation] 気管支喘息発作時の原因ウイルスの同定とサイトカイン産生、好酸球活性化の検討(続報) (2010)
  • Author(s): 加藤政彦,山田佳之,丸山健一,林泰秀
  • Organizer: 第113回日本小児科学会学術集会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-04-23
• [Presentation] 気管支喘息発作時の原因ウイルスの同定とサイトカイン産生、好酸球活性化の検討(続報) (2010)
  • Author(s): 加藤政彦, 山田佳之, 丸山健一, 林泰秀
  • Organizer: 第113回日本小児科学会学術集会
  • Place of Presentation: 盛岡市
  • Year and Date: 2010-04-23
• [Presentation] 新生児・乳児消化管アレルギーの3例 (2010)
  • Author(s): 山田佳之, 江原佳史, 加藤政彦, 林泰秀
  • Organizer: 第113回日本小児科学会学術集会
  • Place of Presentation: 盛岡市
  • Year and Date: 2010-04-23
• [Presentation] Higher frequency of circulating CRTH2+ natural killer T cells in pediatric patients with eosinophilia. (2010)
  • Author(s): Yamada Y, Kourakata K, Kato M, Hayashi Y.
  • Organizer: 66th Annual meeting of American Allergy, Asthma and Immunology
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2010-02-27
• [Presentation] 小児気管支喘息発作時の原因ウイルスの同定とサイトカイン産生および好酸球活性化の検討 (2009)
  • Author(s): 加藤政彦,山田佳之
  • Organizer: 第59回日本アレルギー学会学術大会
  • Place of Presentation: 秋田
  • Year and Date: 2009-10-30
• [Presentation] 小児気管支喘息発作時の原因ウイルスの同定とサイトカイン産生および好酸球活性化の検討 (2009)
  • Author(s): 加藤政彦, 山田佳之
  • Organizer: 第59回日本アレルギー学会学術大会
  • Place of Presentation: 秋田市
  • Year and Date: 2009-10-30
• [Presentation] 好酸球増多をともなったBaraitser-Winter症候群の一例 (2009)
  • Author(s): 山田佳之, 加藤政彦
  • Organizer: 第59回日本アレルギー学会学術大会
  • Place of Presentation: 秋田市
  • Year and Date: 2009-10-29
• [Presentation] 小児気管支喘息発作時の原因ウイルスの同定とサイトカイン/ケモカイン産生および好酸球活性化の検討 (2009)
  • Author(s): 加藤政彦,山田佳之,丸山健一,林泰秀
  • Organizer: 第42回日本小児呼吸器疾患学会
  • Place of Presentation: 高崎
  • Year and Date: 2009-10-18
• [Presentation] 小児気管支喘息発作時の原因ウイルスの同定とサイトカイン/ケモカイン産生および好酸球活性化の検討 (2009)
  • Author(s): 加藤政彦, 山田佳之, 丸山健一, 林泰秀
  • Organizer: 第42回日本小児呼吸器疾患学会
  • Place of Presentation: 高崎市
  • Year and Date: 2009-10-18
• [Presentation] 反復する喀血と肺炎を呈とた先天性中枢性肺胞低換気症候群(CCHS)の一例 (2009)
  • Author(s): 中嶋直樹, 加藤政彦, 村松礼子, 望月博之
  • Organizer: 第42回日本小児呼吸器疾患学会
  • Place of Presentation: 高崎市
  • Year and Date: 2009-10-18
• [Presentation] Different cytokine profile and eosinophil activation are involved in rhinovirus- and respiratory syncytial virus-induced acute exacerbation of childhood wheezing. (2009)
  • Author(s): Kato M, Tsukagoshi H, Yoshizumi M, Saitoh M, Kozawa K, 山田佳之, Maruyama K, 林泰秀, Kimura H
  • Organizer: 6th Biennial International Eosinophil Symposium
  • Place of Presentation: Bruges, Belgium
  • Year and Date: 2009-07-10
• [Presentation] 小児気管支喘息における好酸球活性化および血清中27種類のサイトカイン/ケモカイン産生の検討 (2009)
  • Author(s): 加藤政彦, 山田佳之, 丸山健一, 林泰秀
  • Organizer: アレルギー・好酸球研究会2009
  • Place of Presentation: 東京
  • Year and Date: 2009-06-20
• [Presentation] ウエスト症候群における免疫学的機序に関する研究(第二報) (2009)
  • Author(s): 椎原隆, 渡辺美緒, 山田佳之, 加藤政彦
  • Organizer: 第112回日本小児科学会学術集会
  • Place of Presentation: 奈良市
  • Year and Date: 2009-04-19
• [Presentation] Rhinovirus enhances eosinophil activation through the production of IL-5 in acute exacerbation of childhood asthma. (2009)
  • Author(s): Kato M, Tsukagoshi H, Yoshizumi M, Saitoh M, Kozawa K, 山田佳之, Maruyama K, 林泰秀, Kimura H
  • Organizer: 65th Annual meeting of American Allergy, Asthma and Immunology.
  • Place of Presentation: Washington, DC, USA
  • Year and Date: 2009-03-17
• [Presentation] Rhinovirus enhances eosinophil activation through the production of IL-5 in acute exacerbation of childhood asthma (2009)
  • Author(s): Kato M, Tsukagoshi H, Yoshizumi M, Saitoh M, Kozawa K, Yamada Y, Maruyama K, Hayashi Y, Kimura H.
  • Organizer: 65th Annual meeting of American Allergy, Asthma and Immunology
  • Place of Presentation: Washington, DC, USA
  • Year and Date: 2009-03-17
• [Presentation] Evaluation of cytokine profiles in the secretion from eosinophilic otitis media (2009)
  • Author(s): Uchimizu H, Matsuwaki Y, Kato M, Moriyama H.
  • Organizer: 65th Annual meeting of American Allergy, Asthma and Immunology
  • Place of Presentation: Washington, DC, USA
  • Year and Date: 2009-03-17
• [Presentation] 小児気管支喘息発作時の原因ウイルスの同定とサイトカイン産生および好酸球活性化の検討 (2008)
  • Author(s): 加藤政彦,山田佳之,中嶋直樹,丸山健一,林泰秀
  • Organizer: 第45回日本小児アレルギー学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-12-13
• [Presentation] 家庭用空気清浄機による花粉症抑制効果の検討 (2008)
  • Author(s): 松脇由典, 吉村剛, 浅香大也, 加藤政彦, 大櫛哲史, 小島純也, 黒河圭子, 今井透, 鈴木大輔, 野澤康平, 森山寛
  • Organizer: 第58回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-29
• [Presentation] 小児気管支喘息発作時の原因ウイルスの同定とサイトカイン産生および好酸球活性化の検討-第2報 (2008)
  • Author(s): 加藤政彦, 塚越博之, 齋藤美香, 小澤邦壽, 山田佳之, 丸山健一, 林泰秀, 木村博一
  • Organizer: アレルギー・好酸球研究会2008
  • Place of Presentation: 東京
  • Year and Date: 2008-06-21