ICAR-National Institute of High Security Animal Diseases, Bhopal, Madhya Pradesh, India.
ICAR-National Institute of High Security Animal Diseases, Bhopal, Madhya Pradesh, India.
Cytokine. 2019 Jan;113:21-30. doi: 10.1016/j.cyto.2018.06.002. Epub 2018 Jun 10.
Porcine Reproductive and Respiratory Syndrome (PRRS), caused by PRRS virus (PRRSV), is one of the most important devastating diseases of pigs, characterized by reproductive failure in sows, and respiratory disease with heavy mortality in piglets. PRRS virus has been reported to elevate the levels of proinflammatory cytokines in the serum of infected pigs. High Mobility Group Box-1 (HMGB-1) protein is a cellular biomolecule belonging to the Danger Associated Molecular Patterns (DAMP) family, which stimulates immune cells to release pro-inflammatory cytokines upon release out of cells. The role of HMGB-1 in the pathogenesis of PRRSV remains largely unknown. In the present study, HMGB-1 levels in serum samples collected from six-week-old piglets infected intra-nasally with 2 × 10 TCID/mL of Indian PRRSV (Ind-297221/2013) was estimated by ELISA up to 21 days post infection (dpi). Pro-inflammatory cytokine mRNA (IL-1β, IL-6 and TNF- α) expression in PBL was estimated by SYBR green based real time PCR. Mean HMGB-1 concentration in serum was found to be significantly elevated in PRRSV infected piglets on 6 dpi as compared to uninfected control piglets. At mRNA level, significant increase in expression of HMGB-1 was observed from 4 to 5 dpi and from 11 to 13 dpi. IL-1β and IL-6 mRNA were significantly upregulated between 4 and 6 dpi. Significant increase in TNF-α gene expression was seen only on 7 and 9 dpi. Higher levels of pro-inflammatory cytokines and HMGB-1 could be correlated with fever which was observed within 7 dpi in all the infected piglets and additionally around 13 dpi in the animal that died on 17 dpi. Thus, elevated HMGB-1 level in PRRSV infected piglets could be correlated with concurrent increase in pro-inflammatory cytokine (IL-6) mRNA. In-vitro studies were conducted in PRRSV infected Porcine Pulmonary Alveolar Macrophages (PAM) to ascertain HMGB-1 role in PRRS pathogenesis. The results of both in-vivo and in-vitro studies showed that HMGB-1 plays an important role in mediating the pro-inflammatory cytokine responses in PRRS pathogenesis.
猪繁殖与呼吸综合征（PRRS）由猪繁殖与呼吸综合征病毒（PRRSV）引起，是一种最重要的毁灭性猪病，其特征是母猪繁殖失败，仔猪呼吸疾病死亡率高。据报道，PRRSV 会提高感染猪血清中的促炎细胞因子水平。高迁移率族蛋白 B1（HMGB-1）是一种细胞生物分子，属于危险相关分子模式（DAMP）家族，它在细胞外释放时会刺激免疫细胞释放促炎细胞因子。HMGB-1 在 PRRSV 发病机制中的作用在很大程度上尚不清楚。在本研究中，通过 ELISA 法检测了 6 周龄仔猪经鼻腔感染 2×10 TCID/mL 印度 PRRSV（Ind-297221/2013）后血清样本中 HMGB-1 水平，直至感染后 21 天（dpi）。通过 SYBR green 实时 PCR 法检测了 PBL 中促炎细胞因子 mRNA（IL-1β、IL-6 和 TNF-α）的表达。结果发现，与未感染对照仔猪相比，PRRSV 感染仔猪在 6 dpi 时血清中 HMGB-1 浓度显著升高。在 mRNA 水平上，从 4 到 5 dpi 和从 11 到 13 dpi 观察到 HMGB-1 表达显著增加。IL-1β 和 IL-6 mRNA 从 4 到 6 dpi 显著上调。仅在 7 和 9 dpi 时观察到 TNF-α 基因表达的显著增加。所有感染仔猪在 7dpi 内均出现发热，其中 17dpi 死亡的仔猪在 17dpi 左右还出现发热，感染仔猪中促炎细胞因子和 HMGB-1 水平升高可能与此有关。在 PRRSV 感染的猪肺泡巨噬细胞（PAM）中进行了体外研究，以确定 HMGB-1 在 PRRS 发病机制中的作用。体内和体外研究的结果均表明，HMGB-1 在介导 PRRS 发病机制中的促炎细胞因子反应中起重要作用。
