DICAM-mediated Inhibition of Type 1 Interferon System during Macrophage Differentiation of THP-1 Cells

OBJECTIVE: We have previously shown that DICAM inhibits LPS-mediated macrophage differentiation. However, less is known about the exact action mechanisms of DICAM on the macrophage function and differentiation. METHODS: To induce differentiation into a resting M0 macrophage, THP-1 cells were cultured with 100 nM PMA for 24 h, and then rested for 3 days. THP-1 cells were infected with 50 moi of control LacZ- or DICAM-containing adenovirus. The RNA expression profile associated with DICAM during THP-1 differentiation was analyzed with a microarray chip and in silico analysis with Ingenuity Pathway Analysis (IPA) program. RESULTS: A disease and function analysis of the microarray data in DICAM-overexpressed THP-1 cells revealed a suppression in the expression of multiple genes involved in the response of myeloid cells and phagocytes, and an increase of genes associated with apoptosis of fibroblast cell-line, and viral infection and replication. The canonical pathway analysis also showed the most prominent changes of signaling pathways that involve inflammation responses. An upstream regulator analysis identifyingmolecules upstream of the genes that potentially explain the observed expression changes revealed that IRF7 and the genes in type 1 interferon system, such as IFNA2 and IFNAR,was significantly attenuated by DICAM. A mechanistic network analysis confirmed a direct causal association between IRF7 and type 1 interferon system. A real-time RT-PCR analysis validating the microarray data verified the significant suppression of IRFs, IFNA2, and IFNB1. CONCLUSION: These results suggest that DICAM can be a critical regulator of type 1 interferon system, which is an essential mediator in the process of intracellular infection and systemic lupus erythematosus.

Wernicke's Encephalopathy With Reversible Cortical Involvement

No abstract available.

Delayed-Onset Subdural Hematoma and Oculomotor Nerve Palsy After Improving Spontaneous Intracranial Hypotension

Spontaneous intracranial hypotension (SIH) is a well-known disorder improving with conservative treatment or epidural blood patch in the majority of cases. However, SIH may develop neurological complications such as cranial nerve palsy, subdural hematoma, and altered consciousness. Subdural hematoma in SIH is usually found during intracranial hypotension state and delayed subdural hematoma is rarely reported. We report a case of delayed subdural hematoma and oculomotor nerve palsy after improving spontaneous intracranial hypotension.

Expression patterns of beta ig-h3 in chondrocyte differentiation during endochondral ossification

beta ig-h3 is a TGF-beta-induced extracellular matrix protein which is expressed in many tissues including bones and cartilages. In previous reports, we showed that beta ig-h3 mediates cell adhesion and migration and, especially in bones, negatively regulates the mineralization in the end stage of endochondral ossification. Here, to elucidate the expression pattern and role of beta ig-h3 in chondrocyte differentiation, ATDC5 chondrocytes and embryonic and postnatal mice were used for in vitro differentiation studies and in vivo studies, respectively. beta ig-h3 was strongly induced by the treatment of TGF-beta1 and the expression level of beta ig-h3 mRNA and protein were highly expressed in the early stages of differentiation but decreased in the late stages in ATDC5. Furthermore, the patterns of TGF-beta1, -beta2, and -beta3 mRNA expression were concurrent with beta ig-h3 in ATDC5. beta ig-h3 was deeply stained in perichondrium (PC), periosteum (PO), and prehypertrophic chondrocytes (PH) through the entire period of endochondral ossification in mice. beta ig-h3 was mainly expressed in PC and PH at embryonic days and obviously in PH in postnatal days. These results suggest that beta ig-h3 may play a critical role as a regulator of chondrogenic differentiation in endochondral ossification.