ラット好塩基球性白血病 (RBL-2H3) 細胞の抗原刺激によるタンパク質のチロシンリン酸化と MAPキナーゼ活性化に対する Pemirolast Potassiumの効果 EFFECTS OF AN ANTIALLERGIC DRUG, PEMIROLAST POTASSIUM ON TYROSINE PHOSPHORYLATION AND MAP KINASE ACTIVATION IN ANTIGEN-STIMULATED RAT BASOPHILIC LEUKEMIA (RBL-2H3) CELLS

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Abstract

ラット好塩基球性白血病 (RBL-2H3) 細胞を抗原刺激すると 33, 42, 44, 72, 80, 90, 125kDaのタンパク質がチロシンリン酸化を受けた. その中で42と44kDaのタンパク質は, 抗MAP (mitogenactivated protein)キナーゼ抗体により MAPキナーゼと同定された. 細胞を抗アレギー薬TBX (ペミロラストカリウム)存在下に抗原刺激すると, 濃度依存的 (0.1〜10μg/ml)に33,42と44kDaのタンパク質のチロシンリン酸化が抑制された. 33kDaのタンパク質は, IgE高親和性Fcレセプターのβサブユニットと考えられる. またTBXはホルボールエステルやカルシウムイオノフォアによる MAPキナーゼの活性化も抑制した. しかし, 骨芽球系 (MC3T3-El)細胞ではチロシンリン酸化とMAPキナーゼの活性化に影響がみられなかった. 以上の結果から, TBXはRBL-2H3細胞においてIgE高親和性 Fc レセプター活性化と, カルシウムの動員やCキナーゼ活性化の下流のシグナル伝達分子にも抑制作用を及ぼしている可能性が示唆された.

Aggregation of high affinity IgE Fc receptors (FcεRI) on RBL-2H3 cells results in tyrosine phosphorylation of 33-, 42-, 44-, 72-, 80-, 90-, 125-kDa proteins. The 42 and 44 kDa proteins were identified as mitogen-activated protein (MAP) kinases with immunoblotting of anti-MAP kinase antibody. The effects of an antiallergic drug, pemirolast potassium (TBX) on Ag-induced protein tyrosine phosphorylation and MAP kinase activation were investigated. When RBL-2H3 cells were stimulated with Ag in the presence of TBX, tyrosine phosphorylation of three proteins (33, 42 and 44 kDa) was inhibited concentration-dependently (0.1-10 μg/ml). Inhibition of Ag-induced tyrosine phosphorylation of 33 kDa protein, which could be a β subunit of FcεRI, suggests that TBX may prevent the activation of FcεRI. TBX suppressed activation of MAP kinases (42 and 44 kDa) in response to Ag as well as phorbol myristate acetate (100 nM) or calcium ionophore A23187 (500 nM), implying that the drug acts on signal transduction component(s) between the second messengers and MAP kinases. However, TBX had no effects on protein tyrosine phosphorylation and MAP kinase activation in MC3T3-El osteoblastic cells. These results indicate that TBX may affect FcεRI and also may act as a step distal of Ca^<2+> mobilization and protein kinase C activation leading to MAP kinase activation in RBL-2H3 cells.

Journal

  • Japanese Journal of Allergology

    Japanese Journal of Allergology 44(1), 34-44, 1995

    Japanese Society of Allergology

References:  36

Cited by:  1

Codes

  • NII Article ID (NAID)
    110002423254
  • NII NACSIS-CAT ID (NCID)
    AN00012583
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    0021-4884
  • Data Source
    CJP  CJPref  NII-ELS  J-STAGE 
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