HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fischer, W. H. Articles by Hugli, T. E. Search for Related Content PubMed PubMed Citation Articles by Fischer, W. H. Articles by Hugli, T. E.

Regulation of IL-6 Synthesis in Human Peripheral Blood Mononuclear Cells by C3a and C3a_desArg¹

Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037

The anaphylatoxin C3a has been reported to have immunomodulatory effects on a number of different cell types. In this study we investigated the effects of C3a and C3a_desArg on gene expression and protein secretion of IL-6 in human PBMCs, either alone or in combination with LPS or IL-1ß. C3a or C3a_desArg alone exhibited no effect on the expression or secretion of IL-6. However, when PBMC were stimulated with LPS or IL-1ß, both C3a and C3a_desArg were found to enhance IL-6 release by PBMC in a dose-dependent manner. Since C3a has been shown to induce PGE₂ production by monocytes, and PGE₂ has been shown to influence cytokine production, we investigated the potential role of PGE₂ in C3a-mediated enhancement of LPS- and IL-1ß-induced IL-6 production. Indomethacin blocked PGE₂ release, but had no influence on the observed effects of C3a, suggesting that the effects of C3a on IL-6 production are independent of PGE₂ formation by monocytes. Northern blot analysis showed that C3a as well as C3a_desArg enhanced LPS-induced mRNA levels for IL-6. Pretreatment of PBMCs with pertussis toxin blocked the functions of C3a and C3a_desArg, indicating that the actions of these two molecules are mediated by a G protein-coupled pathway. Furthermore, we investigated the effects of C3a and C3a_desArg on induction of NF-B and activating protein-1 binding. Both molecules enhanced LPS-induced NF-B and activating protein-1 binding activity. These results demonstrate the capacity of intact C3a and its circulating des-Arg form to exert immunmodulatory effects in vitro.

This article has been cited by other articles:

				M. M. Markiewski and J. D. Lambris The Role of Complement in Inflammatory Diseases From Behind the Scenes into the Spotlight Am. J. Pathol., September 1, 2007; 171(3): 715 - 727. [Abstract] [Full Text] [PDF]

				R. Purwar, M. Wittmann, J. Zwirner, M. Oppermann, M. Kracht, O. Dittrich-Breiholz, R. Gutzmer, and T. Werfel Induction of C3 and CCL2 by C3a in Keratinocytes: A Novel Autocrine Amplification Loop of Inflammatory Skin Reactions J. Immunol., October 1, 2006; 177(7): 4444 - 4450. [Abstract] [Full Text] [PDF]

				K. Ritis, M. Doumas, D. Mastellos, A. Micheli, S. Giaglis, P. Magotti, S. Rafail, G. Kartalis, P. Sideras, and J. D. Lambris A Novel C5a Receptor-Tissue Factor Cross-Talk in Neutrophils Links Innate Immunity to Coagulation Pathways J. Immunol., October 1, 2006; 177(7): 4794 - 4802. [Abstract] [Full Text] [PDF]

				S. L. Mueller-Ortiz, T. J. Hollmann, D. L. Haviland, and R. A. Wetsel Ablation of the complement C3a anaphylatoxin receptor causes enhanced killing of Pseudomonas aeruginosa in a mouse model of pneumonia Am J Physiol Lung Cell Mol Physiol, August 1, 2006; 291(2): L157 - L165. [Abstract] [Full Text] [PDF]

				D. Kalant, R. MacLaren, W. Cui, R. Samanta, P. N. Monk, S. A. Laporte, and K. Cianflone C5L2 Is a Functional Receptor for Acylation-stimulating Protein J. Biol. Chem., June 24, 2005; 280(25): 23936 - 23944. [Abstract] [Full Text] [PDF]

				L. Boos, I. L. Campbell, R. Ames, R. A. Wetsel, and S. R. Barnum Deletion of the Complement Anaphylatoxin C3a Receptor Attenuates, Whereas Ectopic Expression of C3a in the Brain Exacerbates, Experimental Autoimmune Encephalomyelitis J. Immunol., October 1, 2004; 173(7): 4708 - 4714. [Abstract] [Full Text] [PDF]

				A. Recinos III, B. K. Carr, D. B. Bartos, I. Boldogh, J. R. Carmical, L. M. Belalcazar, and A. R. Brasier Liver gene expression associated with diet and lesion development in atherosclerosis-prone mice: induction of components of alternative complement pathway Physiol Genomics, September 16, 2004; 19(1): 131 - 142. [Abstract] [Full Text] [PDF]

				C. W. Strey, M. Markiewski, D. Mastellos, R. Tudoran, L. A. Spruce, L. E. Greenbaum, and J. D. Lambris The Proinflammatory Mediators C3a and C5a Are Essential for Liver Regeneration J. Exp. Med., September 15, 2003; 198(6): 913 - 923. [Abstract] [Full Text] [PDF]

				J. M. Inal, B. Schneider, M. Armanini, and J. A. Schifferli A Peptide Derived from the Parasite Receptor, Complement C2 Receptor Inhibitor Trispanning, Suppresses Immune Complex-Mediated Inflammation in Mice J. Immunol., April 15, 2003; 170(8): 4310 - 4317. [Abstract] [Full Text] [PDF]

				D. Kalant, S. A. Cain, M. Maslowska, A. D Sniderman, K. Cianflone, and P. N. Monk The Chemoattractant Receptor-like Protein C5L2 Binds the C3a des-Arg77/Acylation-stimulating Protein J. Biol. Chem., March 21, 2003; 278(13): 11123 - 11129. [Abstract] [Full Text] [PDF]

				C. Monari, T. R. Kozel, F. Bistoni, and A. Vecchiarelli Modulation of C5aR Expression on Human Neutrophils by Encapsulated and Acapsular Cryptococcus neoformans Infect. Immun., July 1, 2002; 70(7): 3363 - 3370. [Abstract] [Full Text] [PDF]

				D. Paparella, T.M. Yau, and E. Young Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update Eur. J. Cardiothorac. Surg., February 1, 2002; 21(2): 232 - 244. [Abstract] [Full Text] [PDF]

				S. M. Drouin, J. Kildsgaard, J. Haviland, J. Zabner, H. P. Jia, P. B. McCray Jr., B. F. Tack, and R. A. Wetsel Expression of the Complement Anaphylatoxin C3a and C5a Receptors on Bronchial Epithelial and Smooth Muscle Cells in Models of Sepsis and Asthma J. Immunol., February 1, 2001; 166(3): 2025 - 2032. [Abstract] [Full Text] [PDF]