Eugenol and isoeugenol, two components of clover oil, have been reported to possess several biomedical properties, such as anti-inflammatory, antimicrobial and antioxidant effects. This study aims to examine the anti-inflammatory effects of eugenol, isoeugenol and four of their derivatives on expression of inducible nitric oxide synthase (iNOS) activated by lipopolysaccharide (LPS) in mouse macrophages (RAW 264.7), and to investigate molecular mechanisms underlying these effects. We found that two derivatives, eugenolol and glyceryl-isoeugenol, had potent inhibitory effects on LPS-induced up regulation of nitrite levels, iNOS protein and iNOS mRNA. In addition, they both suppressed the release of tumor necrosis factor-a (TNF-a) and Interleukin-If (IL-l~) induced by LPS. Moreover, they both attenuated the DNA binding of NF-KB and AP-l, phosphorylation of inhibitory KBa (IKBa), and nuclear translocation of p65 protein induced by LPS. Finally, we demonstrated that glyceryl-isoeugenol suppressed the phosphorylation of ERKl/2, JNK and p38 MAPK, whereas eugenolol suppressed the phosphorylation of ERKl/2 and p38 MAPK. Taken together, these results suggest that that eugenolol and glyceryl-isoeugenol suppress LPS-induced iNOS expression by down-regulating NF-KB and AP-l through inhibition ofMAPKs and AktlIKBa signaling pathways. Thus, this study implies that eugenolol and glyceryl-isoeugenol may provide therapeutic benefits for inflammatory diseases.An expanding body of literature indicates that inducible nitric oxide synthase (iNOS) is a key mediator activated by the inflammatory process and can produce a large amount of NO, causing detrimental effects in patients with chronic inflammation (1-2). Macrophage is one of the most important cells contributing to NO production during inflammatory responses. Expression of the iNOS in macrophages is regulated by many transcriptional factors, including nuclear factor-KB (NF-KB), activator protein-l (AP-l), interferon regulatory factor 1 (IRF1) and signal transducer and activator of transcription I (STATl). In particular,

Defensins are antimicrobial peptides composed of 3 conserved disulfide bridges, a β-sheet, and both hydrophobic and cationic amino acids. In this study, we aimed to demonstrate the immunomodulation role of avian β-defensin 8 ( AvBD8 ) in a chicken macrophage cell line. Chicken AvBD8 stimulated the expression of proinflammatory cytokines (IL-1β, interferon gamma, and IL-12p40) and chemokines (CCL4, CXCL13, and CCL20) in macrophages. Furthermore, by Western blotting and immunocytochemistry, we confirmed that AvBD8 activated the mitogen-activated protein kinase signaling pathway via extracellular regulated kinases 1/2 and p38 signaling molecules. Overall, AvBD8 plays a crucial role in host defense as not only an antimicrobial peptide but also an immunomodulator by activating the mitogen-activated protein kinase signaling pathway and inducing the expression of proinflammatory cytokines and chemokines.

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Objective: The highly pathogenic avian influenza virus (HPAIV) is a threat to the poultry industry as well as the economy and remains a potential source of pandemic infection in humans. Antiviral genes are considered a potential factor for HPAIV resistance. Therefore, in this study, we investigated gene expression related to cytokine-cytokine receptor interactions by comparing resistant and susceptible Ri chicken lines for avian influenza virus infection.Methods: Ri chickens of resistant (Mx/A; BF2/B21) and susceptible (Mx/G; BF2/B13) lines were selected by genotyping the Mx and BF2 genes. These chickens were then infected with HPAIV H5N1, and their lung tissues were collected for RNA sequencing.Results: In total, 972 differentially expressed genes (DEGs) were observed between resistant and susceptible Ri chickens, according to the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. In particular, DEGs associated with cytokinecytokine receptor interactions were most abundant. The expression levels of cytokines (IL-1β, IL-6, IL-8, and IL-18), chemokines (CCL4 and CCL17), interferons (IFN-γ), and IFNstimulated genes (Mx1, CCL19, OASL, and PRK) were higher in H5N1-resistant chickens than in H5N1-susceptible chickens. Conclusion:Resistant chickens show stronger immune responses and antiviral activity (cytokines, chemokines, and IFN-stimulated genes) than those of susceptible chickens against HPAIV infection.