Specificity and reciprocity in the interactions between TGF-beta and macrophage inflammatory protein-1 alpha.
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.
Maltman
J
J
Beatson Institute for Cancer Research, Cancer Research Campaign Beatson Laboratories, Bearsden, Glasgow, U.K.
Pragnell
I B
IB
Graham
G J
GJ
D001854:Bone Marrow Cells; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D003114:Colony-Forming Units Assay; D015870:Gene Expression; D006410:Hematopoiesis; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins; D008264:Macrophages / Q000378:metabolism*; D015846:Monokines / Q000378:metabolism*; D010446:Peptide Fragments; D011498:Protein Precursors; D011506:Proteins / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D054407:Chemokine CCL4; D018946:Chemokine CCL5; D007376:Interleukin-2; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D010446:Peptide Fragments; D011498:Protein Precursors; D011506:Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1