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    • br Funding This work was supported

    2024-03-21


    Funding This work was supported by the National Natural Science Foundation of China (grant No. 81573664). Thanks to Jing-xian Yang from the Pharmacology Laboratory of Liaoning University of Traditional Chinese Medicine for support with technology and experimental equipment.
    Disclosure
    Conflict of Interest
    Authors’ Contributions
    Introduction Since described in USA in 1987, porcine reproductive and respiratory syndrome (PRRS) characterized with respiratory illness in piglets and severe reproductive problems in sows and gilts (Music and Gagnon, 2010) has now been one of the most important diseases in pigs, leading to significant economic losses in swine industry worldwide (Li et al., 2007). PRRS virus (PRRSV) is an enveloped positive single stranded RNA virus and belongs to the genus Arterivirus, family Arteriviridae, order Nidovirales (Cavanagh, 1997). PRRSV genome is approximately 15.4kb in length and has 10 open reading frames (ORFs) (Yun and Lee, 2013). PRRSV exhibits a highly restricted host cell tropism for the Voriconazole of the monocyte/macrophage/dendritic lineages (Duan et al., 1997). Since 2006, there have been devastating outbreaks of atypical PRRS in China, which is characterized by high fever, high morbidity, and high mortality. A highly pathogenic PRRSV (HP-PRRSV) isolate with a 30-amino-acid (30 aa) deletion in non-structural protein (nsp2) was identified as the causative agent (Tian et al., 2007). The acute phase of PRRSV infection primarily targets alveolar macrophages. The mechanistic basis for the acute phase of respiratory distress is likely a consequence of the release of inflammatory cytokines in the lung (Chand et al., 2012). The intensity of the disease appears to vary among isolates and variation in the pathogenicity of PRRSV has been observed in experimentally infected animals (Cho and Dee, 2006, Han et al., 2014). HP-PRRSV is reported to cause severe acute lung injury (Han et al., 2014). The lesions include destruction of lung structure with extensive hemorrhage and a large number of inflammatory cell infiltration into the alveolar spaces. Additionally, interstitial pneumonia also occurs, which is characterized by a marked thickening of the alveolar septa (Shang et al., 2013). Upon infection, neutrophils are always the first to be recruited to the focus and cause capillary leak and pulmonary edema (Segel et al., 2011). Compared with the pigs infected typical PRRSV strains, the number of neutrophils in the lungs of HP-PRRSV-infected pigs was significantly increased (Guo et al., 2013, Han et al., 2014). IL-8 is the main chemokine and activator of neutrophils (Pease and Sabroe, 2002). Upon receiving inflammatory stimuli, IL-8 can be up-regulated in many different cell types, including fibroblasts, monocytes, and hepatocytes (Mukaida, 2000). Thus, we assume that IL-8 production might be induced and be related in the lung lesion upon PRRSV infection (Bohnet et al., 1997, Fujimori et al., 2003, Harada et al., 1994, Hay and Sarau, 2001, Jundi and Greene, 2015, Mukaida et al., 1998).
    Results
    Discussion In this study, we investigated how PRRSV induced IL-8 production. We showed that PRRSV induced IL-8 production in PAMs both in vitro and in vivo. Subsequently, we demonstrated that PRRSV-induced IL-8 production was mainly dependent on the activation of TAK-1/JNK/AP-1 pathways. It was demonstrated that infection with a highly pathogenic strain of PRRSV elicited a significant elevation of cytokines including IL-8 in BALF, serum and TBLN homogenates of pigs (Guo et al., 2013). In our study, we found that PRRSV infection induced IL-8 expression both in vivo and in vitro. Besides, PAMs infected with HP-PRRSV isolate induced higher level of IL-8 expression in PAMs than CH-1a, which is in accordance with another in vivo report (Han et al., 2014). The extensive level of IL-8 and the neutrophils recruited to lungs should be of particular significance in the lung injury. After stimulation by pro-inflammatory cytokines, the activated neutrophils could release free radicals, inflammatory cytokines and proteases, which have contributions to lung lesions (Avasarala et al., 2013, Han et al., 2014, Ware and Matthay, 2000). Indeed, compared with traditional strain, HP-PRRSV isolate can cause much severer neutrophil infiltration and lung lesions (Han et al., 2014, Tian et al., 2007). Therefore, it is reasonable to speculate that upon HP-PRRSV infection macrophages secret higher levels of IL-8, which recruits more neutrophils and eventually leads to tissue damage and dysfunction of the lung.