| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
Chemokines can promote interstitial fibrosis that is, in turn, a
strong predictor of renal failure in chronic glomerulonephritides (GN).
Resident renal cells, including renal tubular epithelial cells (RTEC),
represent a prominent source of chemokine expression. Evaluating those
factors responsible for sustained chemokine production by RTEC during
GN is therefore crucial. The contribution of interstitial T cells to
such expression, and in particular the precise nature of their
interactions with RTEC, are poorly understood. Activated T cell/RTEC
coculture induced production of high levels of monocyte chemoattractant
protein-1 (MCP-1), RANTES, and IFN-inducible protein-10 from RTEC.
Using double-chamber cultures and activated T cell plasma membrane
preparations we demonstrated that both cell contact and soluble factors
contributed to RTEC chemokine production. Importantly, different
chemokines exhibited distinct activation requirements. Thus, for RANTES
cell contact was essential, but not sufficient. In contrast, either
soluble factors or cell contact induced MCP-1 and IFN-inducible
protein-10 production, although both pathways were required for a
maximal response. Neutralization experiments identified critical roles
in this process for proinflammatory cytokines such as TNF-
, IL-1ß,
and IFN-
as well as membrane molecules such as LFA-1, CD40 ligand,
and membrane bound TNF-. Finally, chemotactic bioassays of T
cell/RTEC coculture supernatants demonstrated 80% reduction of
monocyte migration following MCP-1 neutralization, indicating a
dominant role for this chemokine. In summary, activation of renal
tubular cells by infiltrating T cells can amplify and perpetuate local
inflammatory responses through chemokine production differentially
mediated by soluble and cell contact-dependent factors. Recognition of
this regulatory diversity has important implications in the choice of
potential therapeutic targets in GN.
This article has been cited by other articles:
|
|
 |
|
  M. Schaier, S. Vorwalder, C. Sommerer, R. Dikow, F. Hug, M.-L. Gross, R. Waldherr, and M. Zeier Role of FTY720 on M1 and M2 macrophages, lymphocytes, and chemokines in Formula nephrectomized rats Am J Physiol Renal Physiol, September 1, 2009; 297(3): F769 - F780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zheng, R. Sinniah, and S. I-H. Hsu Pathogenic Role of NF-{kappa}B Activation in Tubulointerstitial Inflammatory Lesions in Human Lupus Nephritis J. Histochem. Cytochem., May 1, 2008; 56(5): 517 - 529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kanamaru, S. Pfirsch, M. Aloulou, F. Vrtovsnik, M. Essig, C. Loirat, G. Deschenes, C. Guerin-Marchand, U. Blank, and R. C. Monteiro Inhibitory ITAM Signaling by Fc{alpha}RI-FcR{gamma} Chain Controls Multiple Activating Responses and Prevents Renal Inflammation J. Immunol., February 15, 2008; 180(4): 2669 - 2678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. He, T. R. Schoeb, A. Panoskaltsis-Mortari, K. R. Zinn, R. A. Kesterson, J. Zhang, S. Samuel, M. J. Hicks, M. J. Hickey, and D. C. Bullard Deficiency of P-Selectin or P-Selectin Glycoprotein Ligand-1 Leads to Accelerated Development of Glomerulonephritis and Increased Expression of CC Chemokine Ligand 2 in Lupus-Prone Mice J. Immunol., December 15, 2006; 177(12): 8748 - 8756. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Herrera, A. Ferrebuz, E. G. MacGregor, and B. Rodriguez-Iturbe Mycophenolate Mofetil Treatment Improves Hypertension in Patients with Psoriasis and Rheumatoid Arthritis J. Am. Soc. Nephrol., December 1, 2006; 17(12_suppl_3): S218 - S225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Y. Hoi, M. J. Hickey, P. Hall, J. Yamana, K. M. O'Sullivan, L. L. Santos, W. G. James, A. R. Kitching, and E. F. Morand Macrophage Migration Inhibitory Factor Deficiency Attenuates Macrophage Recruitment, Glomerulonephritis, and Lethality in MRL/lpr Mice J. Immunol., October 15, 2006; 177(8): 5687 - 5696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Laxmanan, D. Datta, C. Geehan, D. M. Briscoe, and S. Pal CD40: A Mediator of Pro- and Anti-Inflammatory Signals in Renal Tubular Epithelial Cells J. Am. Soc. Nephrol., September 1, 2005; 16(9): 2714 - 2723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Castellano, V. Cappiello, N. Fiore, P. Pontrelli, L. Gesualdo, F. P. Schena, and V. Montinaro CD40 Ligand Increases Complement C3 Secretion by Proximal Tubular Epithelial Cells J. Am. Soc. Nephrol., July 1, 2005; 16(7): 2003 - 2011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. de Haij, A. C. Bakker, R. N. van der Geest, G. Haegeman, W. Vanden Berghe, J. Aarbiou, M. R. Daha, and C. van Kooten NF-{kappa}B Mediated IL-6 Production by Renal Epithelial Cells Is Regulated by C-Jun NH2-Terminal Kinase J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1603 - 1611. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P I Sidiropoulos and D T Boumpas Lessons learned from anti-CD40L treatment in systemic lupus erythematosus patients Lupus, May 1, 2004; 13(5): 391 - 397. [Abstract] [PDF]
|
|
|
|
|
|
A.-J. Ruth, A. R. Kitching, T. J. Semple, P. G. Tipping, and S. R. Holdsworth Intrinsic Renal Cell Expression of CD40 Directs Th1 Effectors Inducing Experimental Crescentic Glomerulonephritis J. Am. Soc. Nephrol., November 1, 2003; 14(11): 2813 - 2822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tanaka, T. Kuroiwa, H. Ikeuchi, F. Ota, Y. Kaneko, K. Ueki, Y. Tsukada, I. B. McInnes, D. T. Boumpas, and Y. Nojima Human Platelets Stimulate Mesangial Cells to Produce Monocyte Chemoattractant Protein-1 via the CD40/CD40 Ligand Pathway and May Amplify Glomerular Injury J. Am. Soc. Nephrol., October 1, 2002; 13(10): 2488 - 2496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Inston and P. Cockwell The evolving role of chemokines and their receptors in acute allograft rejection Nephrol. Dial. Transplant., August 1, 2002; 17(8): 1374 - 1379. [Full Text] [PDF]
|
|
|
|
|
|
P. Cockwell, J. W. Calderwood, C. J. Brooks, S. J. Chakravorty, and C. O. S. Savage Chemoattraction of T cells expressing CCR5, CXCR3 and CX3CR1 by proximal tubular epithelial cell chemokines Nephrol. Dial. Transplant., May 1, 2002; 17(5): 734 - 744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Rosenkranz and G. Mayer Proteinuria in the transplanted patient Nephrol. Dial. Transplant., September 1, 2000; 15(9): 1290 - 1292. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
