No abstract

Intercellular adhesion molecule-1 is the adhesion molecule mediating leukocyte firm adhesion to endothelial cells, plays a critical role in subsequent leukocyte transmigration. ICAM-1 is also expressed in other cells including macrophages; however, the role of this adhesion molecule in mediating macrophage functions remains enigmatic. We report that ICAM-1 regulates macrophage polarization by positively modulating miR-124 expression. We found higher expression levels of monocyte chemotactic protein-1 in lungs of mice lacking ICAM-1. Consistent with this result, siRNA mediated depletion of ICAM-1 in macrophage resulted in increased expression levels of MCP-1. Moreover, ICAM-1 controlled miR-124 expression and downregulated MCP-1 mRNA and protein expression by binding of miR-124 to MCP-1 3’ untranslated region. ICAM-1 also induced the transcription factor Sp1 expression, which is important for miR-124 expressing in macrophages. Furthermore, ICAM-1 depletion led to M1 macrophage polarization, in contrast, miR-124 mimics promoted M2 macrophage polarization. Exogenous administration of miR-124 mimics into the lungs prevented lipopolysaccharide-induced myeloperoxidase activity in vivo, suggesting that miR-124 is important for dampening acute lung injury. These results collectively show that adhesion molecule ICAM-1 downregulates MCP-1 expression by controlling Sp1 mediated miR-124 levels, which in turn regulate M2 macrophage polarization. Targeting ICAM-1 and downstream miR-124 may present a new therapeutic strategy for acute lung injury.

Inflammation is the body’s normal self-protection mechanism to eliminate pathogens and resist pathogen invasion. The excessive inflammatory response may lead to inflammatory lesions. The mechanisms accounting for inflammation remain hazy. miRNAs have been proposed to have crucial effects on inflammation. In the present study, we reported that lipopolysaccharide (LPS)-stimulation increased the expression levels of inflammatory cytokines and the cell-cycle progression was suppressed in RAW264.7 cells. Meanwhile, the expression of miR-322 was significantly down-regulated after LPS treatment. Bioinformatics predictions revealed a potential binding site of miR-322 in 3′-UTR of NF-κB1 (p50) and it was further confirmed by luciferase assay. Moreover, both the mRNA and protein levels of NF-κB1 (p50) were down-regulated by miR-322 in RAW264.7 cells. Subsequently, we demonstrated that miR-322 mimics decrease in the expression levels of inflammatory cytokines and cell-cycle repression can be rescued following LPS treatment in RAW264.7 cells. The anti-inflammatory cytokines expression including IL-4 and IL-10 were significantly up-regulated. Furthermore, miR-322 could also promote RAW264.7 cells proliferation. These results demonstrate that miR-322 is a negative regulator of inflammatory response by targeting NF-κB1 (p50).

Antibiotics are widely used for infectious diseases and feed additives for animal health and growth. Antibiotic resistant caused by overuse of antibiotics poses a global health threat. It is urgent to choose safe and environment-friendly alternatives to antibiotics to promote the ecological sustainable development of the pig industry. Phytochemicals are characterized by little residue, no resistance, and minimal side effects and have been reported to improve animal health and growth performance in pigs, which may become a promising additive in pig production. This paper summarizes the biological functions of recent studies of phytochemicals on growth performance, metabolism, antioxidative capacity, gut microbiota, intestinal mucosa barrier, antiviral, antimicrobial, immunomodulatory, detoxification of mycotoxins, as well as their action mechanisms in pig production. The review may provide the theoretical basis for the application of phytochemicals functioning as alternative antibiotic additives in the pig industry.

Aquaporins (AQPs) and Na,K-ATPase control water transport across the air space-capillary barrier in the distal lung and play an important role in the formation and resolution of lung edema. Porcine reproductive and respiratory syndrome virus (PRRSV) infection usually causes pulmonary inflammation and edema in the infected pig lungs. To investigate the possibility that PRRSV infection may cause altered expression of AQPs and Na,K-ATPase messenger RNA (mRNA) levels and protein expression of AQP1, AQP5, and Na,K-ATPase in the PRRSV-infected pig lungs were detected. Quantitative real-time PCR (qRT-PCR) analysis showed markedly decreased mRNA levels of AQP1 and AQP5 and Na,K-ATPase in the PRRSV-infected pig lungs compared to those of uninfected pig lungs. Western blot studies also revealed significantly reduced levels of AQP1, AQP5, and Na,K-ATPase proteins in the PRRSV-infected pig lungs. In addition, immunohistochemical (IHC) analysis showed decreased protein expression of AQP1 and AQP5 in the endothelial cells of the capillaries and venules and secretory cells of terminal bronchiole and the alveolar type I cells, respectively. The expression of Na,K-ATPase in the basolateral membrane of alveolar type II cells presented great reduction in the PRRSV-infected pig lungs. To further understand the reduction of these proteins, the ubiquitination of AQP1 and Na,K-ATPase was examined in uninfected and PRRSV-infected pig lungs. The results showed that there is no difference of ubiquitination for these proteins. Thus, our results suggest that PRRSV infection may induce downregulation of these proteins and cause impairment of edema resolution by failed water clearance in the infected pig lungs.