PPI network and Hubgenes
All DEGs were analyzed by STRING online database. Using the Cytoscape software, 49 DEGs were mapped to the PPI network (Fig 2 ). The top 10 Hub genes referred to IL10, IFNG, Fos, IL19, NPY, Cnr1, PDE4B, MMP13, Rtn1, UCHL1, which were assessed and ranked by the plugin cytoHubba in Cytoscape (Table2). Phosphodiesterase 4B (PDE4B), a member of phosphodiesterase (PDEs) family, serves as a selectively hydrolytic enzyme of second signal messenger cAMP(cyclic adenosine monophosphate)[15,25], playing a vital role in signal transduction of inflammation[15]. The inhibitor of PDE4 has demonstrated a prominent validity in treating inflammatory disease such as asthma, chronic obstructive pulmonary disease, inflammatory bowel disease, atopic dermatitis, rheumatoid arthritis, and other disease[15,26]. cAMP-activated PKA exerts an effect to inhibit NFκB signaling pathway [10,27,28]. PDE4B deficit macrophage exhibit the decreased NFκB activation and reactive oxygen species level induced by LPS, and the suppressed inflammatory response [14,29,30]. The anti-inflammatory ability of NR4a1 has association with NFκB signaling pathway. Therefore, we speculate that NR4a1 may regulate the PED4B expression with anti-inflammatory function and a close relation of NR4a1-regulated PDE4B to cAMP-PKA signaling and NFκB signaling pathway.