Platelet-activating factor exerts mitogenic activity and stimulates expression of interleukin 6 and interleukin 8 in human lung fibroblasts via binding to its functional receptor

doi:10.1084/jem.184.1.191

This Article

	Full Text (PDF, 2136K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Roth, M.
	Articles by Simon, H. U.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Roth, M.
	Articles by Simon, H. U.


Social Bookmarking

	What's this?

ARTICLES

Platelet-activating factor exerts mitogenic activity and stimulates expression of interleukin 6 and interleukin 8 in human lung fibroblasts via binding to its functional receptor

M Roth, M Nauck, S Yousefi, M Tamm, K Blaser, AP Perruchoud and HU Simon
Department of Internal Medicine, University Hospital, Basel, Switzerland.

Platelet-activating factor (PAF) is a potent proinflammatory phospholipid mediator of the lung. In this study, we demonstrate that PAF receptor mRNA and protein is expressed by human lung fibroblasts. Interaction of PAF with its specific receptor resulted in increases of tyrosine phosphorylation of several intracellular proteins, indicating that the PAF-receptor might be functionally active. PAF-induced transcription of protooncogenes c-fos and c-jun as well as of interleukin (IL)-6 and IL-8 genes in human fibroblasts. Transcription of the interleukins was followed by secretion of the respective proteins. Moreover, PAF enhanced proliferation of fibroblasts in a concentration-dependent manner. Using signaling inhibitors, we demonstrate that PAF-induced transcription of the c-fos, IL-6, and IL-8 genes, as well as proliferation, require activation of pertussis toxin- sensitive G proteins, tyrosine kinases, and protein kinase C (PKC). In contrast, transcription of c-jun was blocked by pertussis toxin, but not by inhibitors for tyrosine kinases or PKC. These data suggest that PAF stimulates distinct signaling pathways in human lung fibroblasts. In addition, the activation of human fibroblasts by PAF leads to enhanced proliferation and to the expression of proinflammatory cytokines, which may contribute to the pathophysiological changes in pulmonary inflammation.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Karakiulakis, G., Papakonstantinou, E., Aletras, A. J., Tamm, M., Roth, M. (2007). Cell Type-specific Effect of Hypoxia and Platelet-derived Growth Factor-BB on Extracellular Matrix Turnover and Its Consequences for Lung Remodeling. J. Biol. Chem. 282: 908-915 [Abstract] [Full Text]
Cheng, L., Cao, W., Fiocchi, C., Behar, J., Biancani, P., Harnett, K. M. (2006). HCl-induced inflammatory mediators in cat esophageal mucosa and inflammatory mediators in esophageal circular muscle in an in vitro model of esophagitis. Am. J. Physiol. Gastrointest. Liver Physiol. 290: G1307-G1317 [Abstract] [Full Text]
Melnikova, V. O., Mourad-Zeidan, A. A., Lev, D. C., Bar-Eli, M. (2006). Platelet-activating Factor Mediates MMP-2 Expression and Activation via Phosphorylation of cAMP-response Element-binding Protein and Contributes to Melanoma Metastasis. J. Biol. Chem. 281: 2911-2922 [Abstract] [Full Text]
Ibe, B. O., Portugal, A. M., Chaturvedi, S., Raj, J. U. (2005). Oxygen-dependent PAF receptor binding and intracellular signaling in ovine fetal pulmonary vascular smooth muscle. Am. J. Physiol. Lung Cell. Mol. Physiol. 288: L879-L886 [Abstract] [Full Text]
Venkatesha, R. T., Ahamed, J., Nuesch, C., Zaidi, A. K., Ali, H. (2004). Platelet-activating Factor-induced Chemokine Gene Expression Requires NF-{kappa}B Activation and Ca2+/Calcineurin Signaling Pathways: INHIBITION BY RECEPTOR PHOSPHORYLATION AND {beta}-ARRESTIN RECRUITMENT. J. Biol. Chem. 279: 44606-44612 [Abstract] [Full Text]
Cummings, R. J., Parinandi, N. L., Zaiman, A., Wang, L., Usatyuk, P. V., Garcia, J. G. N., Natarajan, V. (2002). Phospholipase D Activation by Sphingosine 1-Phosphate Regulates Interleukin-8 Secretion in Human Bronchial Epithelial Cells. J. Biol. Chem. 277: 30227-30235 [Abstract] [Full Text]
Bihl, M. P., Heinimann, K., Rudiger, J. J., Eickelberg, O., Perruchoud, A. P., Tamm, M., Roth, M. (2002). Identification of a Novel IL-6 Isoform Binding to the Endogenous IL-6 Receptor. Am. J. Respir. Cell Mol. Bio. 27: 48-56 [Abstract] [Full Text]
Ahamed, J., Ali, H. (2002). Distinct Roles of Receptor Phosphorylation, G Protein Usage, and Mitogen-activated Protein Kinase Activation on Platelet Activating Factor-induced Leukotriene C4 Generation and Chemokine Production. J. Biol. Chem. 277: 22685-22691 [Abstract] [Full Text]
Marques, S. A., Dy, L. C., Southall, M. D., Yi, Q., Smietana, E., Kapur, R., Marques, M., Travers, J. B., Spandau, D. F. (2002). The Platelet-Activating Factor Receptor Activates the Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase and Induces Proliferation of Epidermal Cells through an Epidermal Growth Factor-Receptor-Dependent Pathway. J. Pharmacol. Exp. Ther. 300: 1026-1035 [Abstract] [Full Text]
NAGASE, T., ISHII, S., SHINDOU, H., OUCHI, Y., SHIMIZU, T. (2002). Airway Hyperresponsiveness in Transgenic Mice Overexpressing Platelet Activating Factor Receptor Is Mediated by an Atropine-Sensitive Pathway. Am. J. Respir. Crit. Care Med. 165: 200-205 [Abstract] [Full Text]
Sugano, T., Narahara, H., Nasu, K., Arima, K., Fujisawa, K., Miyakawa, I. (2001). Effects of platelet-activating factor on cytokine production by human uterine cervical fibroblasts. Mol Hum Reprod 7: 475-481 [Abstract] [Full Text]
McKay, S., Hirst, S. J., Haas, M. B.-d., de Jongste, J. C., Hoogsteden, H. C., Saxena, P. R., Sharma, H. S. (2000). Tumor Necrosis Factor-alpha Enhances mRNA Expression and Secretion of Interleukin-6 in Cultured Human Airway Smooth Muscle Cells. Am. J. Respir. Cell Mol. Bio. 23: 103-111 [Abstract] [Full Text]
Sugano, T., Nasu, K., Narahara, H., Kawano, Y., Nishida, Y., Miyakawa, I. (2000). Platelet-Activating Factor Induces an Imbalance Between MatrixMetalloproteinase-1 and Tissue Inhibitor of Metalloproteinases-1 Expressionin Human Uterine Cervical Fibroblasts. Biol. Reprod. 62: 540-546 [Abstract] [Full Text]
Merendino, N., Dwinell, M. B., Varki, N., Eckmann, L., Kagnoff, M. F. (1999). Human intestinal epithelial cells express receptors for platelet-activating factor. Am. J. Physiol. Gastrointest. Liver Physiol. 277: G810-G818 [Abstract] [Full Text]
Dy, L. C., Pei, Y., Travers, J. B. (1999). Augmentation of Ultraviolet B Radiation-induced Tumor Necrosis Factor Production by the Epidermal Platelet-activating Factor Receptor. J. Biol. Chem. 274: 26917-26921 [Abstract] [Full Text]
Zidovetzki, R., Chen, P., Chen, M., Hofman, F.M. (1999). Endothelin-1-Induced Interleukin-8 Production in Human Brain-Derived Endothelial Cells Is Mediated by the Protein Kinase C and Protein Tyrosine Kinase Pathways. Blood 94: 1291-1299 [Abstract] [Full Text]
Bastien, Y., Toledano, B. J., Mehio, N., Cameron, L., Lamoukhaid, B., Renzi, P., Hamid, Q., Mazer, B. D. (1999). Detection of Functional Platelet-Activating Factor Receptors on Human Tonsillar B Lymphocytes. J. Immunol. 162: 5498-5505 [Abstract] [Full Text]
Eickelberg, O., Pansky, A., Mussmann, R., Bihl, M., Tamm, M., Hildebrand, P., Perruchoud, A. P., Roth, M. (1999). Transforming Growth Factor-beta 1 Induces Interleukin-6 Expression via Activating Protein-1 Consisting of JunD Homodimers in Primary Human Lung Fibroblasts. J. Biol. Chem. 274: 12933-12938 [Abstract] [Full Text]
Bihl, M., Tamm, M., Nauck, M., Wieland, H., Perruchoud, A. P., Roth, M. (1998). Proliferation of Human Non-Small-Cell Lung Cancer Cell Lines: Role of Interleukin-6. Am. J. Respir. Cell Mol. Bio. 19: 606-612 [Abstract] [Full Text]
Tamm, M., Bihl, M., Eickelberg, O., Stulz, P., Perruchoud, A. P., Roth, M. (1998). Hypoxia-Induced Interleukin-6 and Interleukin-8 Production Is Mediated by Platelet-Activating Factor and Platelet-Derived Growth Factor in Primary Human Lung Cells. Am. J. Respir. Cell Mol. Bio. 19: 653-661 [Abstract] [Full Text]
Pei, Y., Barber, L. A., Murphy, R. C., Johnson, C. A., Kelley, S. W., Dy, L. C., Fertel, R. H., Nguyen, T. M., Williams, D. A., Travers, J. B. (1998). Activation of the Epidermal Platelet-Activating Factor Receptor Results in Cytokine and Cyclooxygenase-2 Biosynthesis. J. Immunol. 161: 1954-1961 [Abstract] [Full Text]
Barber, L. A., Spandau, D. F., Rathman, S. C., Murphy, R. C., Johnson, C. A., Kelley, S. W., Hurwitz, S. A., Travers, J. B. (1998). Expression of the Platelet-activating Factor Receptor Results in Enhanced Ultraviolet B Radiation-induced Apoptosis in a Human Epidermal Cell Line. J. Biol. Chem. 273: 18891-18897 [Abstract] [Full Text]
Levan, T. D., Bloom, J. W., Adams, D. G., Hensel, J. L., Halonen, M. (1998). Platelet-Activating Factor Induction of Activator Protein-1 Signaling in Bronchial Epithelial Cells. Mol. Pharmacol. 53: 135-140 [Abstract] [Full Text]
Kume, K., Shimizu, T. (1997). Platelet-activating Factor (PAF) Induces Growth Stimulation, Inhibition, and Suppression of Oncogenic Transformation in NRK Cells Overexpressing the PAF Receptor. J. Biol. Chem. 272: 22898-22904 [Abstract] [Full Text]
HERRERO-BEAUMONT, G, EGIDO, J (1997). PAF, a potent proinflammatory mediator, looking for its role in the pathogenesis of joint damage. Ann Rheum Dis 56: 211-213 [Full Text]