Mouse Anti-Human CD30 monoclonal antibody, clone JID141

A role of inflammation-associated cytokines/chemokines has been implicated in a wide variety of human diseases. Here, we investigated the regulation of inflammatory cytokines released by monocyte-derived THP-1 cells following treatment with the dietary agent withaferin A (WFA). Membrane-based cytokine array profiling of the culture supernatant from adenosine triphosphate-stimulated WFA-treated THP-1 cells showed differential regulation of multiple cytokines/chemokines. A selected group of cytokines/chemokines [interleukin-1 beta (IL-1 beta), CCL2/MCP-1, granulocyte-macrophage colony stimulating factor, PDGF-AA, PTX3, cystatin-3, relaxin-2, TNFRSF8/CD30, and ACRP30] was validated at the transcription level using qPCR. In silico analysis for transcriptional binding factors revealed the presence of nuclear factor-kappa B (NF-kappa B) in a group of down-regulated cytokine gene promoters. WFA treatment of THP-1 cells blocks the nuclear translocation of NF-kB and corresponds with the reduced levels of cytokine secretion. To further understand the differential expression of cytokines/chemokines, we showed that WFA alters the nigericin-induced co-localization of NLRP3 and ASC proteins, thereby inhibiting caspase-1 activation, which is responsible for the cleavage and maturation of pro-inflammatory cytokines IL-1 beta and IL-18. These data suggest that dietary agent WFA concurrently targets NF-kappa B and the inflammasome complex, leading to inhibition of IL-1 beta and IL-18, respectively, in addition to differential expression of multiple cytokines/chemokines. Taken together, these results provide a rationale for using WFA to further explore the anti-inflammatory mechanism of cytokines/chemokines associated with inflammatory diseases.

Marek's disease is a viral neoplastic disease of chickens caused by Marek's disease virus (MDV). Gene expression patterns have been investigated at different MDV infection stages, but there is limited research about the late tumor transformation phase. In this experiment, 44K Agilent chicken genomewide expression micromays were used to profile differential expression in tumorous spleens (TS) from severely morbid chickens and apparently normal spleens from survivors (SS) after MDV infection and expression in noninfected spleens (NS) from controls. There were 4,317 differentially expressed (DE) genes in TS versus NS. However, no DE genes were detected in SS versus NS, suggesting that maintenance of, or return to, homeostasis of gene activity in survivor spleens. Down-regulated genes in tumorous spleens mainly enriched in the cytokine-cytokine receptor interaction pathway, and commonly investigated genes in Marek's disease study, IL6, IL18, IFNA, and IFNG were nondifferentially expressed, which indicates host inflammatory response was impaired. The IL10 and TNFRSF8 genes were upregulated in tumorous spleens. We speculated that 1110 might be exploited by MDV to escape from host immune surveillance, as reported for Epstein-Barr virus, which stimulated T cells secreting IL10 to subvert immune response. Previous study reported that transcription from TNFRSF8 promoter could be enhanced by MDV oncogene Meq. In this study, the increased expression of TNFRSF8 indicated interaction between MDV and TNFRSF8, which might facilitate pathogenesis and tumor transformation. The expression of many members in IGF system was changed in tumorous compared with noninfected spleens. The downregulation of IGFBP7 was considered to be associated with MD lymphoma transformation. Gene expression change of multiple regulatory pathways indicated their involvements in facilitating tumor transformation.