Hyperactivation of the epidermal growth factor receptor (EGFR) pathways and chronic inflammation are common characteristics of oral squamous cell carcinoma (OSCC). Previously, we reported that OSCC cells secrete interleukin-1 beta (IL-1β), which promotes the proliferation of the oral premalignant cell line, DOK, and stimulates DOK and OSCC cells to produce the chemokine CXCL1. CXCL1 functions through CXCR2, a G protein-coupled receptor that transactivates EGFR in ovarian and lung cancers. We hypothesized that IL-1β transactivates EGFR through the CXCL1–CXCR2 axis in OSCC. In this study, we demonstrated that tyrosine phosphorylation of EGFR is crucial for the IL-1β-mediated proliferation and subsequent bromodeoxyuridine (BrdU) incorporation of DOK cells because the EGFR inhibitors AG1478 and erlotinib inhibit these abilities in a dose-dependent manner. Addition of IL-1β instantly enhanced CXCL1 expression and secretion (within 15 min) in the DOK and OSCC cell lines. Furthermore, tyrosine phosphorylation of EGFR was significantly enhanced in DOK (1 h) and OSCC (20 min) cell lines after IL-1β treatment, and both cell lines were inhibited on the addition of an IL-1 receptor antagonist (IL-1Ra). CXCL1 treatment resulted in EGFR phosphorylation, whereas the knockdown of CXCL1 expression by lentivirus-mediated shRNA or the addition of the CXCR2 antagonist SB225002 dramatically reduced IL-1β-mediated EGFR phosphorylation and proliferation of DOK cells. Neutralizing antibodies against IL-1β or CXCL1 markedly inhibited the constitutive or IL-1β-induced tyrosine phosphorylation of EGFR in OSCC cells. IL-1β transactivates EGFR through the CXCL1-CXCR2 axis, revealing a novel molecular network in OSCC that is associated with autocrine IL-1β and EGFR signaling.

Sensorineural hearing loss (SNHL) is a prevalent form of deafness commonly arising from damage to the cochlear sensory hair cells and degeneration of the spiral ganglion neurons. In this study, Sendai virus was used to generate an induced pluripotent stem cell (iPSC) line from a 39-year-old female patient diagnosed with severe-to-profound, non-syndromic SNHL. The patient also carries a A1555G mutation in the mitochondrial 12S ribosome RNA gene (MTRNR1). This iPSC line was verified to express pluripotent markers, possess normal karyotype, harbor the specific mutation and demonstrated the capacity to differentiate into three germ layers.

Leucine rich repeat kinase (LRRK2) is the most prevalent genetic cause for Parkinson's disease. LRRK2 p.G2385R is an Asian specific genetic risk factor for sporadic Parkinson's disease. We generated two induced pluripotent stem cells (iPSCs), IBMS-iPSC-018-09 and IBMS-iPSC-020-01, from the peripheral blood mononuclear cells of two patients carrying LRRK2 p.G2385R variant by using the Sendai-virus delivery system. These iPSCs had a normal karyotype and exhibited pluripotency, such as an embryonic stem cell-like morphology, expression of pluripotent markers, and capacity to differentiate into three germ layers. This cellular model will provide a platform for pathophysiological studies of neurodegeneration in Parkinson's disease.

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Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative disease caused by a trinucleotide repeat (CAG) expansion in the coding region of ATXN3 gene resulting in production of ataxin-3 with an elongated polyglutamine tract. Here, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cells of a male patient with SCA3 by using the Sendai-virus delivery system. The resulting iPSCs had a normal karyotype, retained the disease-causing ATXN3 mutation, expressed pluripotent markers and could differentiate into the three germ layers. Potentially, the iPSCs could be a useful tool for the investigation of disease mechanisms of SCA3.