The Journal of Immunology, Vol 156, Issue 4 1566-1571, Copyright © 1996 by American Association of Immunologists

ARTICLES

Specificity and reciprocity in the interactions between TGF-beta and macrophage inflammatory protein-1 alpha

J Maltman, IB Pragnell and GJ Graham
Beatson Institute for Cancer Research, Cancer Research Campaign Beatson Laboratories, Bearsden, Glasgow, U.K.

TGF-beta and macrophage inflammatory protein-1 alpha (MIP-1 alpha) appear to share a number of biologic properties. We have been attempting to examine the interactions between these two peptides in the hope of gaining an insight into the basis for the apparent functional redundancy. Our earlier observations have indicated that TGF- beta is a potent down-regulator of MIP-1 alpha and MIP-1 beta expression in bone marrow macrophages and also of MIP-1 alpha receptor numbers on FDCPmix cells. We now demonstrate that the interplay between TGF-beta and MIP-1 alpha beta is relatively specific, in that only MIP- 1 alpha and MIP-1 beta appear to be potently suppressed by TGF-beta, and that this suppressive activity is restricted to the direct TGF-beta isoforms. Activin and the bone morphogenetic proteins (BMPs) appear to be inactive in this regard. We also demonstrate the existence of an endogenous TGF-beta-mediated block that acts to minimize MIP-1 alpha expression in TGF-beta-expressing macrophages. This coupled with the observations that MIP-1 alpha can induce expression of TGF-beta suggests to us that the complex interactions between MIP-1 alpha and MIP-1 beta and the direct TGF-beta isoforms (beta 1, beta 2, and beta 3) act to ensure minimized MIP-1 alpha beta expression and maximized TGF-beta expression. However, such interplay may also be dependent on the local cytokine or inflammatory profile to which the cells are exposed.

This article has been cited by other articles:

				H. W. van Deventer, W. O'Connor Jr., W. J. Brickey, R. M. Aris, J. P.Y. Ting, and J. S. Serody C-C Chemokine Receptor 5 on Stromal Cells Promotes Pulmonary Metastasis Cancer Res., April 15, 2005; 65(8): 3374 - 3379. [Abstract] [Full Text] [PDF]

				Y. Zhang, L. L. McCormick, S. R. Desai, C. Wu, and A. C. Gilliam Murine Sclerodermatous Graft-Versus-Host Disease, a Model for Human Scleroderma: Cutaneous Cytokines, Chemokines, and Immune Cell Activation J. Immunol., March 15, 2002; 168(6): 3088 - 3098. [Abstract] [Full Text] [PDF]

				L. Rothe, P. Collin-Osdoby, Y. Chen, T. Sunyer, L. Chaudhary, A. Tsay, S. Goldring, L. Avioli, and P. Osdoby Human Osteoclasts and Osteoclast-Like Cells Synthesize and Release High Basal and Inflammatory Stimulated Levels of the Potent Chemokine Interleukin-8 Endocrinology, October 1, 1998; 139(10): 4353 - 4363. [Abstract] [Full Text] [PDF]

				C. M. McManus, C. F. Brosnan, and J. W. Berman Cytokine Induction of MIP-1{alpha} and MIP-1{beta} in Human Fetal Microglia J. Immunol., February 1, 1998; 160(3): 1449 - 1455. [Abstract] [Full Text] [PDF]