From the *Division of Nephrology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung; †Department of Nursing, MeiHo University, Pingtung; ‡Division of Cardiac Surgery, Department of Surgery, §Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University; ∥Department of Pediatrics, E-DA Hospital, I-Shou University; ¶Department of Marine Biotechnology and Resources, National Sun Yat-sen University; **Graduate Institute of Medicine, College of Medicine, ††Department of Pediatrics, Kaohsiung Medical University Hospital, and Department of Pediatrics, Faculty of Pediatrics, College of Medicine, Kaohsiung Medical University; ‡‡Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung; §§Department of Radiation Oncology, ∥∥Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University, and ¶¶Department of Pediatrics, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China.
J Investig Med. 2014 Feb;62(2):332-9. doi: 10.2310/JIM.0000000000000042.
Inflammation plays critical roles in atherosclerosis. Chemokines are responsible for leukocyte trafficking and involve in inflammatory diseases. Macrophage inflammatory protein 1α (MIP-1α) has been implicated in atherosclerotic lesion formation. Prostaglandin I2 (PGI2) analog, used in pulmonary hypertension, has been reported to have anti-inflammatory functions. However, little is known about its role in the MIP-1α production in human monocytes.
We investigated the effects of 3 conventional (iloprost, beraprost, and treprostinil) and 1 new (ONO-1301) PGI2 analogs, on the expression of MIP-1α expression in human monocytes. Human primary monocytes from control subjects and THP-1 cell line were treated with PGI2 analogs, with or without lipopolysaccharide (LPS) stimulation. Supernatants were harvested to measure MIP-1α levels by enzyme-linked immunosorbent assay. To explore which receptors involved the effects of PGI2 analogs on the expression of MIP-1α expression, I prostanoid (IP) and E prostanoid, peroxisome proliferator-activated receptor (PPAR)-α, and PPAR-r receptor antagonists were used to pretreat THP-1 cells. Forskolin, a cyclic adenosine monophosphate (cAMP) activator, was also used to further confirm the cAMP involvement on the effect of PGI2 analogs in MIP-1α production.
Three PGI2 analogs could suppress LPS-induced MIP-1α production in THP-1 cells and human primary monocytes. ONO-1301 had a similar effect. CAY 10449, an IP receptor antagonist, could reverse the suppressive effects on MIP-1α production of iloprost. Forskolin, a cAMP activator, also suppressed MIP-1α production in THP-1 cells.
Prostaglandin I2 analogs suppressed LPS-induced MIP-1α production in human monocytes via the IP receptor and cAMP pathway. The PGI2 analog may be potential in the treatment for atherosclerosis.
炎症在动脉粥样硬化中起着关键作用。趋化因子负责白细胞的迁移，并参与炎症性疾病。巨噬细胞炎性蛋白 1α（MIP-1α）已被牵连到动脉粥样硬化病变的形成中。前列腺素 I2（PGI2）类似物，用于治疗肺动脉高压，据报道具有抗炎作用。然而，关于其在人单核细胞中 MIP-1α产生中的作用知之甚少。
我们研究了 3 种传统（伊洛前列素、贝前列素和曲前列素）和 1 种新型（ONO-1301）PGI2 类似物对人单核细胞中 MIP-1α表达的影响。用 PGI2 类似物处理对照受试者和 THP-1 细胞系的人原代单核细胞，有或没有脂多糖（LPS）刺激。收获上清液通过酶联免疫吸附测定法测量 MIP-1α 水平。为了探讨 PGI2 类似物对 MIP-1α 表达的影响涉及哪些受体，我们使用 I 型前列腺素（IP）和 E 型前列腺素、过氧化物酶体增殖物激活受体（PPAR）-α 和 PPAR-r 受体拮抗剂预处理 THP-1 细胞。还使用forskolin（一种环磷酸腺苷（cAMP）激活剂）进一步证实 cAMP 参与 PGI2 类似物对 MIP-1α 产生的影响。
三种 PGI2 类似物可抑制 LPS 诱导的 THP-1 细胞和人原代单核细胞中 MIP-1α 的产生。ONO-1301 也有类似的效果。IP 受体拮抗剂 CAY 10449 可逆转伊洛前列素对 MIP-1α 产生的抑制作用。forskolin（一种 cAMP 激活剂）也抑制了 THP-1 细胞中 MIP-1α 的产生。
前列腺素 I2 类似物通过 IP 受体和 cAMP 途径抑制 LPS 诱导的人单核细胞中 MIP-1α 的产生。PGI2 类似物可能在动脉粥样硬化的治疗中有潜力。
