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Interleukin-1alpha enhances IL-8 secretion through p38 mitogen-activated protein kinase and reactive oxygen species signaling in human pancreatic cancer cells.
Med Sci Monit. 2005 Oct; 11(10):BR343-50.MS

Abstract

BACKGROUND

Interleukin (IL)-1alpha 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-1alpha 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-kappaB (NF-kappaB) was determined by Western blot. Involvement of reactive oxygen species (ROS) were examined by measuring the H2O2. Activity of activator factor-1 (AP-1) and NF-kappaB 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-1alpha 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-1alpha also induced production of ROS. Exogenous H2O2 enhanced IL-8 secretion and N-acetyl cysteine (NAC) prevented IL-1alpha-induced ROS production and IL-8 secretion. EMSA confirmed that IL-1alpha increased DNA-binding activity of AP-1 and NF-kappaB. Inhibitors and ROS scavenger studies revealed that upstream signalings for AP-1 and NF-kappaB were MAPK and ROS, respectively. Conditioned media from pancreatic cancer cells pretreated with IL-1alpha remarkably stimulated in vitro HUVECs growth.

CONCLUSIONS

These results suggest that MAPK/AP-1 and ROS/NF-kappaB signaling pathways are involved in IL-1alpha-induced IL-8 secretion and that these paracrine signaling pathways enhance endothelial cell proliferation.

Authors+Show Affiliations

Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, Japan. cb8h-swi@asahi-net.or.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16192891

Citation

Sawai, Hirozumi, et al. "Interleukin-1alpha Enhances IL-8 Secretion Through P38 Mitogen-activated Protein Kinase and Reactive Oxygen Species Signaling in Human Pancreatic Cancer Cells." Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, vol. 11, no. 10, 2005, pp. BR343-50.
Sawai H, Funahashi H, Okada Y, et al. Interleukin-1alpha enhances IL-8 secretion through p38 mitogen-activated protein kinase and reactive oxygen species signaling in human pancreatic cancer cells. Med Sci Monit. 2005;11(10):BR343-50.
Sawai, H., Funahashi, H., Okada, Y., Matsuo, Y., Sakamoto, M., Yamamoto, M., Takeyama, H., & Manabe, T. (2005). Interleukin-1alpha enhances IL-8 secretion through p38 mitogen-activated protein kinase and reactive oxygen species signaling in human pancreatic cancer cells. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, 11(10), BR343-50.
Sawai H, et al. Interleukin-1alpha Enhances IL-8 Secretion Through P38 Mitogen-activated Protein Kinase and Reactive Oxygen Species Signaling in Human Pancreatic Cancer Cells. Med Sci Monit. 2005;11(10):BR343-50. PubMed PMID: 16192891.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-1alpha enhances IL-8 secretion through p38 mitogen-activated protein kinase and reactive oxygen species signaling in human pancreatic cancer cells. AU - Sawai,Hirozumi, AU - Funahashi,Hitoshi, AU - Okada,Yuji, AU - Matsuo,Yoichi, AU - Sakamoto,Masaki, AU - Yamamoto,Minoru, AU - Takeyama,Hiromitsu, AU - Manabe,Tadao, Y1 - 2005/09/26/ PY - 2005/06/15/received PY - 2005/08/01/accepted PY - 2005/9/30/pubmed PY - 2006/1/24/medline PY - 2005/9/30/entrez SP - BR343 EP - 50 JF - Medical science monitor : international medical journal of experimental and clinical research JO - Med Sci Monit VL - 11 IS - 10 N2 - BACKGROUND: Interleukin (IL)-1alpha 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-1alpha 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-kappaB (NF-kappaB) was determined by Western blot. Involvement of reactive oxygen species (ROS) were examined by measuring the H2O2. Activity of activator factor-1 (AP-1) and NF-kappaB 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-1alpha 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-1alpha also induced production of ROS. Exogenous H2O2 enhanced IL-8 secretion and N-acetyl cysteine (NAC) prevented IL-1alpha-induced ROS production and IL-8 secretion. EMSA confirmed that IL-1alpha increased DNA-binding activity of AP-1 and NF-kappaB. Inhibitors and ROS scavenger studies revealed that upstream signalings for AP-1 and NF-kappaB were MAPK and ROS, respectively. Conditioned media from pancreatic cancer cells pretreated with IL-1alpha remarkably stimulated in vitro HUVECs growth. CONCLUSIONS: These results suggest that MAPK/AP-1 and ROS/NF-kappaB signaling pathways are involved in IL-1alpha-induced IL-8 secretion and that these paracrine signaling pathways enhance endothelial cell proliferation. SN - 1234-1010 UR - https://www.unboundmedicine.com/medline/citation/16192891/Interleukin_1alpha_enhances_IL_8_secretion_through_p38_mitogen_activated_protein_kinase_and_reactive_oxygen_species_signaling_in_human_pancreatic_cancer_cells_ L2 - https://www.medscimonit.com/download/index/idArt/430275 DB - PRIME DP - Unbound Medicine ER -