01 October 2005
Interleukin-1α enhances IL-8 secretion through p38 mitogen-activated protein kinase and reactive oxygen species signaling in human pancreatic cancer cells
Hirozumi Sawai, Hitoshi Funahashi, Yuji Okada, Yoichi Matsuo, Yoichi Matsuo, Masaki Sakamoto, Minoru Yamamoto, Hiromitsu Takeyama, Tadao ManabeMed Sci Monit 2005; 11(10): BR343-350 :: ID: 430275
Abstract
Background:Interleukin (IL)-1α plays an important role in modulating the expression of various growth factors and angiogenic factors in tumor cells. In here, we investigated effect of IL-1α on IL-8 secretion in human pancreatic cancer cells and underlying signal transduction pathways.Material/Methods:IL-8 expression and secretion by pancreatic cancer cells was measured by Western blot and enzyme-linked immunosorbent assay (ELISA), respectively. Activation of extracellular signal regulated kinases-1/2 (ERK-1/2), p38 mitogen-activated protein kinase (MAPK), c-jun aminoterminal kinase, Akt, and nuclear factor-κB (NF-κB) was determined by Western blot. Involvement of reactive oxygen species (ROS) were examined by measuring the H[sub]2[/sub]O[sub]2[/sub]. Activity of activator factor-1 (AP-1) and NF-κB was examined by electrophoretic mobility sift assay (EMSA). Proliferation of human umbilical vein endothelial cells (HUVECs) was determined by the 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide dye reduction method and cell count.Results:IL-1α modulated IL-8 secretion and induced activation of ERK-1/2 and p38 MAPK. Specific inhibitors for MEK-1 and p38 MAPK suppressed IL-8 secretion. IL-1α also induced production of ROS. Exogenous H[sub]2[/sub]O[sub]2[/sub] enhanced IL-8 secretion and N-acetyl cysteine (NAC) prevented IL-1α-induced ROS production and IL-8 secretion. EMSA confirmed that IL-1α increased DNA-binding activity of AP-1 and NF-κB. Inhibitors and ROS scavenger studies revealed that upstream signalings for AP-1 and NF-κB were MAPK and ROS, respectively. Conditioned media from pancreatic cancer cells pretreated with IL-1α remarkably stimulated in vitro HUVECs growth.Conclusions:These results suggest that MAPK/AP-1 and ROS/NF-κB signaling pathways are involved in IL-1α -induced IL-8 secretion and that these paracrine signaling pathways enhance endothelial cell proliferation.
Keywords: Electrophoretic Mobility Shift Assay, Culture Media, Conditioned, Blotting, Western, Enzyme-Linked Immunosorbent Assay, Interleukin-1 - physiology, Interleukin-8 - secretion, Pancreatic Neoplasms - pathology, Signal Transduction - physiology, Transcription Factor AP-1 - metabolism, Tumor Cells, Cultured, p38 Mitogen-Activated Protein Kinases - metabolism
Editorial
01 March 2024 : Editorial
Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent β-ThalassemiaDOI: 10.12659/MSM.944204
Med Sci Monit 2024; 30:e944204
In Press
18 Mar 2024 : Clinical Research
Sexual Dysfunction in Women After Tibial Fracture: A Retrospective Comparative StudyMed Sci Monit In Press; DOI: 10.12659/MSM.944136
21 Feb 2024 : Clinical Research
Potential Value of HSP90α in Prognosis of Triple-Negative Breast CancerMed Sci Monit In Press; DOI: 10.12659/MSM.943049
22 Feb 2024 : Review article
Differentiation of Native Vertebral Osteomyelitis: A Comprehensive Review of Imaging Techniques and Future ...Med Sci Monit In Press; DOI: 10.12659/MSM.943168
23 Feb 2024 : Clinical Research
A Study of 60 Patients with Low Back Pain to Compare Outcomes Following Magnetotherapy, Ultrasound, Laser, ...Med Sci Monit In Press; DOI: 10.12659/MSM.943732
Most Viewed Current Articles
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952