Modulation of Fibroblast Functions by Interleukin 1: Increased Steady-State Accumulation of Type I Procollagen Messenger RNAs and Stimulation of Other Functions but Not Chemotaxis


Interleukin-I (IL-1) is synthesized by and released from macrophages in response to a variety of stimuli and appears to play an essential role in virtually all inflammatory conditions. In tissues of mesenchymal origin (e.g., cartilage, muscle, bone, and soft connective tissue) I L l induces changes characteristic of both destructive as well as reparative phenomena. Previous studies with natural IL-1 of varying degrees of purity have suggested that it is capable of modulating a number of biological activities of fibroblasts. We have compared the effects of purified human recombinant (hr) IL-la and !~ on several fibroblast functions. The parameters studied include cell proliferation, chemotaxis, and production of collagen, collagenase, tissue inhibitor of metalloproteinase (TIMP), and prostaglandin (PG) E2. We observed that hrlL-ls stimulate the synthesis and accumulation of type I procollagen chains. Intracellular degradation of collagen is not altered by the hrlL-ls. Both IL-ls were observed to increase the steady-state levels of pro al(I) and pro a2(I) mRNAs, indicating that they exert control of type I procollagen gene expression at the pretranslational level. We found that both hrlL-la and 13 stimulate synthesis of TIMP, collagenase, PGE2, and growth of fibroblasts in vitro but are not chemotactic for fibroblasts. Although hrlL-la and 13 both are able to stimulate production of PGE2 by fibroblasts, inhibition of prostaglandin synthesis by indomethacin has no measurable effect on the ability of the IL-ls to stimulate cell growth or production of collagen and collagenase. Each of the IL-ls stimulated proliferation and collagen production by fibroblasts to a similar degree, however hrlL-113 was found to be less potent than hrlL-1 a in stimulating PGE2 production. These observations support the notion that IL-l~t and 13 may both modulate the degradation of collagen at sites of tissue injury by virtue of their ability to stimulate collagenase and PGE2 production by fibroblasts. Furthermore, IL-la and 13 might also direct reparative functions of fibroblasts by stimulating their proliferation and synthesis of collagen and TIMP. S TUDIES with natural interleukin-1 (IL-t) ~ of varying degrees of purity have suggested that this monokine may play a pivotal role in modulating the biological activities of a variety of target cells. Effects attributed to IL-1 on immune and inflammatory cells have been previously reviewed (26). Several other factors named for a specific biological activity now appear to be identical or related to IL-1; these include endogenous pyrogen, leukocyte endogenous 1. Abbreviations used in this paper: hrlL-la and I$, human recombinant a and 13; IL-1, interleukin 1; PGE2, prostaglandin E2; TIMP, tissue inhibitor of metalloproteinase. mediators, catabolin, mononuclear cell factor, and proteolysis inducing factor (26). The biological activities of mesenchymal cells involved in the synthesis and maintenance of the extracellular matrix are affected by IL-1. IL-1 promotes growth of fibroblasts and osteoblasts and increases alkaline phosphatase production by the latter (15, 27). Dermal fibroblasts, adherent synovial cells, and chondrocytes produce increased quantities of collagenase when they are treated with IL l (14, 23, 28). Natural and recombinant ILqs also stimulate hyaluronic acid production by fibroblasts (AEP; submitted for publication). Preparations of natural IL-1 have also been shown to stimulate prostaglandin E2 (PGE2) production by synoviocytes and 9 The Rockefeller University Press, 0021-9525/88/02/311/8 $2.00 The Journal of Cell Biology, Volume 106, February 1988 311-318 311 on A ril 8, 2017 D ow nladed fom Published February 1, 1988

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@inproceedings{Stricklin2002ModulationOF, title={Modulation of Fibroblast Functions by Interleukin 1: Increased Steady-State Accumulation of Type I Procollagen Messenger RNAs and Stimulation of Other Functions but Not Chemotaxis}, author={George P. Stricklin and Helen Poppleton}, year={2002} }