IL-17F Induces CCL20 in Bronchial Epithelial Cells

IL-17F plays a crucial role in airway inflammatory diseases including asthma, but its function has not been fully elucidated. CCL20 is also involved in allergic airway inflammation, while its regulatory mechanisms remain to be defined. To further identify a novel role of IL-17F, the expression of CCL20 by IL-17F in bronchial epithelial cells and the signaling mechanisms involved were investigated. Bronchial epithelial cells were stimulated with IL-17F, and the levels of CCL20 gene and protein measured, with the effects of the addition of various kinase inhibitors and siRNAs also investigated. IL-17F significantly induced the expression of CCL20 gene and protein. Pretreatment with inhibitors for MEK1/2, Raf1 and MSK1, and overexpression of a Raf1 dominant-negative mutant significantly diminished IL-17F-induced CCL20 production. Moreover, transfection of the siRNAs targeting MSK1, p90RSK, and CREB blocked CCL20 expression. These findings suggest that IL-17F is able to induce CCL20 via Raf1-MEK1/2-ERK1/2-MSK1/p90RSK-CREB signaling pathway in bronchial epithelial cells. The IL-17F/CCL20 axis may be a novel pharmacological target for asthma

Paradoxical response to osimertinib therapy in a patient with T790M‑mutated lung adenocarcinoma

A ‘paradoxical response’ to cancer treatment is a term used to describe the emergence of unexpected new lesions and the progression of existing lesions, despite appropriate and effective therapy. ‘Pseudo‑progression’ is a phenomenon in which lymphocytes activated by an immune checkpoint inhibitor accumulate in a tumor and expand its shadow, mimicking enlargement of the primary lesion or development of a new metastatic lesion. Patients receiving cancer chemotherapy may respond differently to treatment, by exhibiting a response, deterioration, or the simultaneous occurrence of both. These variations may be attributed to the heterogeneity of the cancer. However, differences in the temporary response to epidermal growth factor receptor‑tyrosine kinase inhibitor (EGFR‑TKI) treatment are rarely observed. If such a phenomenon is observed, it should not affect the evaluation of the therapeutic effect or be considered as an indication for the discontinuation of treatment. We herein report a rare case of a transient increase in carcinomatous pleural fluid as a paradoxical response to osimertinib treatment in a patient with T790M‑mutated lung adenocarcinoma. The primary lesion and pulmonary metastases responded well to therapy. Although this paradoxical response is very rare, of non‑malignant nature, and does not usually require treatment modification of, physicians must acknowledge that it is not a clinically discouraging characteristic when using EGFR‑TKI to treat T790M‑mutated lung adenocarcinoma

Elevated serum levels of two anti-neutrophil cytoplasmic antibodies in a lung cancer patient: A case report

A 71-year-old woman with arthralgia and lung fibrosis was referred to Mito Kyodo General Hospital (Mito, Japan) for a mass, which was incidentally observed on a chest radiograph. The chest computed tomography scan demonstrated fibrotic lesions in the lower lobes of the lung and a nodule in the left upper lobe. The serum levels of myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) and proteinase 3 (PR3)-ANCA were 60.3 and 7.5 U/ml, respectively. A transbronchial biopsy obtained from the nodule in the left upper lobe of the lung revealed a lung adenocarcinoma and the patient underwent standard upper lobectomy of the left lung. Subsequent to the resection, the serum levels of PR3-ANCA and MPO-ANCA returned to 10.0 and <1.0 U/ml, respectively. Notably, titers of antinuclear antibodies were also decreased during the postoperative course. Although elevated serum ANCA levels are rarely seen in lung cancer, they may be associated with the occurrence of lung cancer in certain patients, as observed in the present case

Superficial‑type endobronchial metastases from colon cancer : A case report

Certain internal malignancies, including colon cancer, can develop endobronchial metastasis. The present study reports a case of colon cancer with superficial‑type endobronchial metastases in a 76‑year‑old male. Chest computed tomography revealed small masses and infiltrates in each lung, with bilateral hilar lymph node swelling. Superficial endobronchial tumors in each of the bronchi were unexpectedly found by bronchoscopic examination. A biopsy specimen obtained from the endobronchial tumor was diagnosed as colon cancer. Superficial‑type endobronchial metastasis from colon cancer is extremely rare, however, such metastasis should be considered for patients who have a history of colon cancer. There should be no hesitation in performing a bronchoscopic biopsy as an additional examination

Cross-talk between TLR3 and TNF-α or IFN-γ Signaling in Induction of CXCL8/IL-8 and CXCL10/IP-10 Expression in Airway Epithelial Cells

CXCL8/IL-8 is a chemoattractant for neutrophils and mast cells, and regulates inflammatory cell recruitment in allergy, infection, and other neutrophil-related diseases. Interferon (IFN) -γ-inducible protein 10 (CXCL10/IP-10) is a chemokine that attracts mononuclear cells, Th1 cells, and natural killer cells. We investigated the levels of CXCL8/IL-8 and CXCL10/IP-10 expression by airway epithelial cells after exposure to the inflammatory cytokines tumor necrosis factor (TNF) -α and IFN-γ, and to poly I:C, a synthetic analog of double-stranded RNA that is a ligand of Toll-like receptor 3 (TLR3). Poly I:C, TNF-α, IFN-γ, and combinations of poly I:C with TNF-α or IFN-γ were used to stimulate the airway epithelial cell line BEAS-2B. Following stimulation, we determined CXCL8/IL-8 and CXCL10/IP-10 mRNA levels by real-time PCR and protein levels by ELISA. Poly I:C treatment upregulated mRNA and protein expression for both CXCL8/IL-8 and CXCL10/IP-10. The addition of TNF-α, but not IFN-γ, to poly I:C further increased the expression of CXCL8/IL-8 mRNA and protein. The addition of either TNF-α or IFN-γ to the poly I:C treatment further increased CXCL10/IP-10 mRNA and protein expression. Cross-talk between TLR3 signaling and inflammatory cytokines regulates the expression of CXCL8/IL-8 and CXCL10/IP-10 in airway epithelial cells. From our results, TNF-α and IFN-γ produce different effects on TLR3 signaling

Current evidence for a modulation of low back pain by human genetic variants

The manifestation of chronic back pain depends on structural, psychosocial, occupational and genetic influences. Heritability estimates for back pain range from 30% to 45%. Genetic influences are caused by genes affecting intervertebral disc degeneration or the immune response and genes involved in pain perception, signalling and psychological processing. This inter-individual variability which is partly due to genetic differences would require an individualized pain management to prevent the transition from acute to chronic back pain or improve the outcome. The genetic profile may help to define patients at high risk for chronic pain. We summarize genetic factors that (i) impact on intervertebral disc stability, namely Collagen IX, COL9A3, COL11A1, COL11A2, COL1A1, aggrecan (AGAN), cartilage intermediate layer protein, vitamin D receptor, metalloproteinsase-3 (MMP3), MMP9, and thrombospondin-2, (ii) modify inflammation, namely interleukin-1 (IL-1) locus genes and IL-6 and (iii) and pain signalling namely guanine triphosphate (GTP) cyclohydrolase 1, catechol-O-methyltransferase, μ opioid receptor (OPMR1), melanocortin 1 receptor (MC1R), transient receptor potential channel A1 and fatty acid amide hydrolase and analgesic drug metabolism (cytochrome P450 [CYP]2D6, CYP2C9)

Long-term safety of budesonide/formoterol for the treatment of elderly patients with bronchial asthma

The long-term safety of budesonide/formoterol (BUD/FM) inhalation has not been fully evaluated, particularly in elderly patients with bronchial asthma. To evaluate the 12-month safety of BUD/FM inhalation for elderly asthmatic patients, the changes in serum potassium levels and pulse rate were examined. A retrospective chart review was conducted of consecutive patients who were treated with BUD/FM inhalation (two inhalations of 160/4.5 mg, twice daily; Symbicort Turbuhaler, AstraZeneca) at a hospital between February 2010 and January 2012. A total of 350 patients were treated with BUD/FM inhalation during the study period and were followed up over 12 months. The mean age of the patients was 60 years, and 19.4% and 21.4% of the patients were aged 65-74 years and ≥75 years, respectively. One hundred and fourteen (32.6%) of the 350 patients continued the inhalation therapy for >12 months. Compared with the pretreatment data, reductions in serum potassium levels at 1, 6 and 12 months were not observed, even in the patients aged 65-74 and ≥75 years. There was also no increase in the pulse rate at 1, 6 and 12 months, even in the patients aged 65-74 and ≥75 years. The usual dosage of BUD/FM showed no adverse effects on the serum potassium levels and pulse rate in the adults, including the elderly with persistent asthma

Ossification and increased bone mineral density with zoledronic acid in a patient with lung adenocarcinoma: A case report

Cases of ossification and increased bone mineral density (BMD) at sites of bone metastasis following zoledronic acid (ZA) treatment have not been reported. The current study presents the case of a 65‑year‑old patient with lung adenocarcinoma and bone metastases in the lumbar vertebrae and femurs. Ossification and an increase in BMD at the metastatic sites was achieved following treatment with ZA and irradiation of the bone metastatic sites. The patient was able to maintain a normal lifestyle for over two years, despite the bone metastases. Therefore, as treatment with ZA was demonstrated to improve patient quality of life, physicians should consider this treatment strategy, particularly for the treatment of metastasis in weight‑bearing bones