線維芽細胞増殖因子（FGF）シグナル伝達は、炎症反応を調節することで急性膵炎誘発性の損傷から保護する

Fibroblast Growth Factor (FGF) Signaling Protects Against Acute Pancreatitis-Induced Damage by Modulating Inflammatory Responses.

• Hai-Jian Tu
• Cheng-Fei Zhao
• Zhi-Wei Chen
• Wei Lin
• Yu-Cai Jiang

抄録

背景 急性膵炎（AP）は、突然の膵臓の炎症の症状であり、患者に重篤な苦痛を与えます。一般的に、AP発症時には線維芽細胞増殖因子（FGF）レベルが上昇し、アミラーゼやリパーゼ活性が上昇しますが、タンパク質濃度は低くなっています。しかし、FGFシグナルがAP発症を制御するメカニズムは未だ解明されていない。酵素免疫吸着法を用いて、AP発症群と健常対照群の血清中のPGE2, TNF-α, sCRP, FGF1, FGF2の濃度を測定した。また、血清試料中のIkappaBalpha及びp-IkappaBalphaレベルを分析した。その後、ＡＰラットモデルを確立し、ＡＰラットにＦＧＦ１抗体、ＦＧＦ２抗体、抗ＦＧＦ１抗体、抗ＦＧＦ２抗体、Ｂａｙ１１-７０８２を注射した。TNF-α、PAI-1 JNK、p-JNK、IkappaBalpha、およびp-IkappaBalphaのレベルも調べた。結果 結果は、PGE2、TNF-α、sCRP、p-IkappaBalpha、FGF1、FGF2、アミラーゼおよびリパーゼ活性のレベルが健康な人と比較してAP患者で増加していることを示した。また、蛋白質濃度は健常者に比べてAP患者では低かった。また、FGF1またはFGF2を注射してFGFシグナルを活性化すると、膵臓でのAP誘発性炎症反応が抑制され、アミラーゼ活性やリパーゼ活性、タンパク質濃度が上昇した。しかし、FGF1抗体及びFGF2抗体の注入は、血清中のAP介在性炎症反応を加速させた。また、Bay11-7082の注射は、APによる炎症反応の活性化とアミラーゼおよびリパーゼ活性を抑制した。タンパク質濃度もAPラットで増加した。結論 FGF シグナルは AP 活性化炎症反応を阻害することで AP 介在性の損傷から保護する。

BACKGROUND Acute pancreatitis (AP) is a symptom of sudden pancreas inflammation, which causes patients severe suffering. In general, fibroblast growth factor (FGF) levels are increased and amylase and lipase activities are elevated during AP pathogenesis, but protein concentration are low. However, the mechanism through which FGF signaling regulates AP pathogenesis remains elusive. MATERIAL AND METHODS The concentrations of PGE2, TNF-alpha, sCRP, FGF1, and FGF2 in the serum samples of the AP group and healthy control group were detected by enzyme-linked immunosorbent assay. In addition, IkappaBalpha and p-IkappaBalpha levels were analyzed in the serum samples. Subsequently, the AP rat model was established, and FGF1, FGF2, anti-FGF1, and anti-FGF2 antibodies and Bay11-7082 were injected into AP rats. TNF-alpha, PAI-1 JNK, p-JNK, IkappaBalpha, and p-IkappaBalpha levels were also examined. RESULTS Results showed that levels of PGE2, TNF-alpha, sCRP, p-IkappaBalpha, FGF1, and FGF2, as well as amylase and lipase activity were increased in patients with AP compared with those in healthy people. In addition, protein concentrations were lower in patients with AP than in the healthy group. Activation of FGF signaling by injecting FGF1 or FGF2 also inhibited AP-induced inflammation response in the pancreas and increased amylase and lipase activities, as well as protein concentration. However, the injection of FGF1 and FGF2 antibodies accelerated AP-mediated inflammation responses in the serum. In addition, Bay11-7082 injection inhibited AP activation of inflammation response and amylase and lipase activities. Protein concentration were also increased in AP rats. CONCLUSIONS FGF signaling protects against AP-mediated damage by inhibition of AP-activating inflammatory responses.