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 by human recombinant interleukin 1 alpha and beta

Abstract

Abstract. 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) ILl 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.

Collagen production by macrophages in tumour encapsulation and dormancy

“…It has already been demonstrated that unspecified lymphocyte products (Johnson & Ziff, 1976;Postlethwaite et al, 1984), unspecified T-cell products (Wahl & Gately, 1983), interleukin-l, which is produced by many cells including T-cells (Goldring & Krane, 1987;Postlethwaite et al, 1988), and transforming growth factor beta, produced by T-cells and macrophages (Roberts et al, 1986;Raghow et al, 1987), influence collagen production by cultured fibroblasts. The depletion of T-cells inhibited the formation of bacterial cell wall-induced hepatic granulomas in vivo (Wahl et al, 1986), and reduced the ability of immune spleen cells to form granulomas around Schistosoma eggs in vitro (Bentley et al, 1982).…”

The role of P2X7 receptors in tissue fibrosis: a brief review

“…In vitro studies demonstrate that IL-1β can stimulate collagen expression in a dose-dependent manner [48]. Because IL-1β can induce its own gene expression, chronic activation of the inflammasome resulting in the continual cleavage of IL-1β in a positive feedback mechanism could conceivably maintain a high level of active TGF-β1 protein resulting in fibrosis [49].…”

Liposomal IGF-1 gene transfer modulates pro- and anti-inflammatory cytokine mRNA expression in the burn wound

“…35 IL-1 and TNF-␣ have been shown to upregulate the expression of matrix metalloproteinases (MMPs) in fibroblasts, especially MMP-1 and MMP-3. 36,37 In general, MMPs favor the degradation of extracellular matrix, with its collagen, laminin and basal membrane components, thus slowing deposition of the necessary cellular matrix, wound closure and re-epithelialization.…”

“…The IGF-1 modulation of the cytokine release after burn trauma appears to contribute to the observed improvement in wound healing. 34,35 The IGF-1 effects on inflammatory and anti-inflammatory cytokine expression may also influence extracellular matrix deposition and thus improve eventual wound breaking strength. 10,31 Although, there were significant differences in the local cytokine mRNA levels in burned animals after treatment with IGF-1 cDNA gene transfer compared with untreated burn animals, systemic serum cytokine levels for TNF-␣, IL-1␤, and IL-6 proteins did not show any significant changes in either treated or untreated burned rats.…”