天然化合物抑制人類微小病毒B19誘導巨噬細胞發炎反應機制之研究

人類微小病毒B19 (Parvovirus B19，B19V) 感染通常具有自限性，主要在幼童、孕婦以及免疫力低下的患者造成疾病。許多研究發現B19病毒與心肌炎、肝炎、關節炎等發炎性疾病相關。目前臨床上以靜脈注射免疫球蛋白(Intravenous immunoglobulin，IVIG)的治療方式為主，但IVIG僅為暫時性限制病毒感染，無法完全清除體內的病毒。因此本研究希望從天然化合物中找尋候選潛能藥物。先前許多文獻證實天然化合物雷公藤紅素可抑制脂多醣(LPS)所誘發的巨噬細胞發炎反應，因此本研究探討雷公藤紅素是否具有抑制人類微小病毒B19誘導巨噬細胞發炎反應及作用機制。研究結果顯示脂多醣(LPS)、B19殼體蛋白VP1獨立區域(B19V-VP1u)及非結構蛋白(B19V-NS1)可促進人類巨噬細胞U937發炎反應，包括細胞遷移、MMP-9活性與發炎相關蛋白質、促發炎細胞激素IL-6、TNFα、IL-1β等表現增加。而雷公藤紅素在無細胞毒性的濃度下能透過p38/ERK MAPK訊息傳遞路徑有效降低脂多醣(LPS)、B19V-VP1u和B19V-NS1誘導U937巨噬細胞發炎反應。

Human Parvovirus B19 infection (B19V) is usually self-limiting, and it mainly causes diseases in young children, pregnant women, and patients with weakened immunity. Many studies have found that the B19V is related to inflammatory diseases such as myocarditis, hepatitis, and arthritis. At present, intravenous immunoglobulin (IVIG) is the main treatment in clinic, but IVIG only temporarily limits the virus infection and cannot eliminate the virus in the body. Therefore, this study hopes to find potential drugs from natural compounds. Many studies have confirmed that the natural compound Celastrol can inhibit the inflammatory response of macrophages induced by lipopolysaccharide (LPS). Therefore, this study will explore whether Celastrol can inhibit B19V-induced inflammation of macrophages and its mechanism. Research results show that lipopolysaccharide (LPS), B19V-VP1 unique region, and a non-structural protein (B19V-NS1) can promote the inflammation response of human macrophages U937, including migration, MMP-9 activity, inflammation-related proteins, and pro-inflammatory cytokines IL-6, TNFα, IL-1β. Celastrol can effectively reduce LPS, B19V-VP1u and B19V-NS1 induced inflammation of macrophages through the p38/ERK MAPK signaling pathway.