Department of Biological Science, College of Medical and Life Sciences, Silla University, 140 Baegyang-daero, 700beon-gil, Sasang-gu, Busan 617-736, Republic of Korea.
Department of Periodontology, School of Dentistry, Pusan National University, 49 Busandaehak-ro, Mulgeum-eup, Yangsan, Gyeongsangnam-do 626-870, Republic of Korea; Dental Research Institute, Pusan National University Dental Hospital, Yangsan, Gyeongsangnam-do, Republic of Korea; Dental and Life Science Institute, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
Int Immunopharmacol. 2019 Oct;75:105750. doi: 10.1016/j.intimp.2019.105750. Epub 2019 Jul 19.
Telmisartan, widely prescribed for the treatment of hypertension, has an anti-inflammatory property in addition to being an angiotensin II type 1 receptor antagonist. This study was carried out to explore the influence of telmisartan upon the elaboration of inflammatory mediators in murine macrophages stimulated with lipopolysaccharide (LPS) prepared from Prevotella intermedia, a periodontal pathogen, as well as its molecular mechanisms. Telmisartan significantly inhibited LPS-induced generation of inducible nitric oxide (NO) synthase-derived NO and interleukin-1β (IL-1β) as well as their gene expressions in RAW264.7 cells. Telmisartan treatment of LPS-activated cells significantly up-regulated arginase 1 (Arg-1) and chitinase-like 3 (Ym-1), which are specific markers of M2 macrophages. Telmisartan caused a significant increase in heme oxygenase-1 (HO-1) expression in cells stimulated with LPS, and its inhibitory action against NO production was reversed by treatment with SnPP, an HO-1 inhibitor. Phosphorylation of STAT1 and STAT3 induced by LPS was attenuated by telmisartan. Telmisartan inhibited LPS-induced generation of NO and IL-1β independently of PPAR-γ activation. In addition, activation of NF-κB as well as JNK and p38 signaling induced by LPS was not modulated by telmisartan. In summary, telmisartan is a potent inhibitor of P. intermedia LPS-induced generation of NO and IL-1β in RAW264.7 cells and promotes macrophage phenotype switching toward the M2 phenotype. Telmisartan may have potential to be developed into host modulatory agent for inflammatory periodontal disease, although additional studies are needed to confirm the therapeutic effect.
替米沙坦除了作为血管紧张素 II 型 1 型受体拮抗剂外，还具有抗炎作用，被广泛用于治疗高血压。本研究旨在探讨替米沙坦对牙周病病原体中间普雷沃菌脂多糖（LPS）刺激的小鼠巨噬细胞中炎症介质产生的影响及其分子机制。替米沙坦可显著抑制 LPS 诱导的 RAW264.7 细胞中诱导型一氧化氮合酶衍生的一氧化氮（NO）和白细胞介素-1β（IL-1β）的产生及其基因表达。替米沙坦处理 LPS 激活的细胞可显著上调精氨酸酶 1（Arg-1）和几丁质酶样蛋白 3（Ym-1），这是 M2 巨噬细胞的特异性标志物。替米沙坦可显著增加 LPS 刺激的细胞中血红素加氧酶-1（HO-1）的表达，其对 NO 产生的抑制作用可被 HO-1 抑制剂 SnPP 逆转。LPS 诱导的 STAT1 和 STAT3 磷酸化被替米沙坦减弱。替米沙坦可抑制 LPS 诱导的 NO 和 IL-1β的产生，而不依赖于 PPAR-γ 激活。此外，替米沙坦不能调节 LPS 诱导的 NF-κB 以及 JNK 和 p38 信号通路的激活。综上所述，替米沙坦是一种有效的 P. intermedia LPS 诱导的 RAW264.7 细胞中 NO 和 IL-1β产生的抑制剂，并促进巨噬细胞向 M2 表型转化。替米沙坦可能具有成为治疗炎症性牙周病的宿主调节因子的潜力，尽管还需要进一步的研究来确认其治疗效果。
