JNJ-7777120はヒスタミンH4受容体(H4R: Ki = 4.5nM)拮抗剤である[1]。JNJ-7777120は、骨髄由来の肥満細胞(BMMCs)が抗原刺激の下でのCCL17とCCL22の産生を阻害でき、よって炎症反応を減らし、皮膚炎の症状を改善する[2]。JNJ-7777120は主に、炎症と脳損傷の緩和に使われる[3]。
ヒト末梢血好中球で、JNJ-7777120 (0.001, 0.01, 0.1, 1, 10μM；30分間)は特異的にH4受容体を拮抗し、好中球の脱顆粒機能を回復させ、H4受容体が炎症プロセスの阻害で負の規制的役割を果たしていることを検証する[4]。Th17細胞で、JNJ-7777120 (10μM；1時間)の添加後、細胞IL-17分泌の傾向は阻害された[5]。
軽度外傷性脳損傷(mTBI)ラットモデルで、JNJ-7777120 (1mg/kg；腹腔内；2回/日、7日間)の処理は、ラットで、軽度TBIによる運動感覚反射とバランス機能の損傷を著しく軽減した[6]。ラットアレルギー喘息モデルで、JNJ-7777120 (20mg/kg；皮下；単回注射)は喘息の症状を軽減できる[7]。LPSマウスモデルで、JNJ-7777120 (5, 10, 20mg/kg；経口；単回投与)の処理は、TNFレベルを減らした[8]。
References:
[1]. Thurmond RL, Desai PJ, Dunford PJ, et al. A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties. The Journal of pharmacology and experimental therapeutics. 2004 Apr 1; 309(1): 404-413.
[2]. Ohsawa Y, Hirasawa N. The antagonism of histamine H 1 and H 4 receptors ameliorates chronic allergic dermatitis via anti‐pruritic and anti‐inflammatory effects in NC/N ga mice. Allergy. 2012 Aug; 67(8): 1014-1022.
[3]. Correa MF, dos Santos Fernandes JP. Targeting the Histamine H4 Receptor: Future Drugs for Inflammatory Diseases. Current Organic Chemistry. 2018 Jul 1; 22(17): 1663-1672.
[4]. Dib K, Perecko T, Jenei V, et al. The histamine H4 receptor is a potent inhibitor of adhesion-dependent degranulation in human neutrophils. Journal of Leukocyte Biology. 2014 Sep; 96(3): 411-418.
[5]. Han SH, Hur MS, Kim MJ, et al. Preliminary study of histamine H4 receptor expressed on human CD4+ T cells and its immunomodulatory potency in the IL-17 pathway of psoriasis. Journal of dermatological science. 2017 Oct 1; 88(1): 29-35.
[6]. Saglam-Cifci E, Gulec I, Sengelen A, et al. The H4R antagonist, JNJ-7777120 treatments ameliorate mild traumatic brain injury by reducing oxidative damage, inflammatory and apoptotic responses through blockage of the ERK1/2/NF-kB pathway in a rat model. Experimental Neurology. 2025 Mar 1; 385: 115133.
[7]. Beermann S, Glage S, Jonigk D, et al. Opposite effects of mepyramine on JNJ 7777120-induced amelioration of experimentally induced asthma in mice in sensitization and provocation. PloS one. 2012 Jan 17; 7(1): e30285.
[8]. Cowden JM, Yu F, Challapalli M, et al. Antagonism of the histamine H 4 receptor reduces LPS-induced TNF production in vivo. Inflammation Research. 2013 Jun; 62: 599-607.