Collagen: Structure, function, and metabolism in normal and fibrotic tissues

Local corticosteroid injection treatment in rheumatic disorders.

The ability of vitamin A to reverse the inhibitory effects of chronic corticosteroids on cutaneous and fascial wound healing is well established. To investigate this in the unique low-collagen environment of the intestinal anastomosis, 35 rabbits received twice-daily injections of either saline (control), dexamethasone (0.1 mg/kg/day), dexamethasone plus low-dose vitamin A (1,000 IU/kg/day), or dexamethasone plus high-dose vitamin A (10,000 IU/kg/day) for a 2-week period. Animals then underwent creation of single-layer, inverting small and large intestine anastomoses. All injections were continued postoperatively. A fifth group received only dexamethasone preoperatively and dexamethasone plus high-dose vitamin A postoperatively. On postoperative day 7, animals underwent in situ assessment of anastomotic bursting pressure and subsequent histologic examination using a modified Ehrlich/Hunt scale. Corticosteroids significantly impaired the healing of small and large intestine anastomoses, with decreased bursting pressures and histologic parameters at 1 week. Only high-dose vitamin A significantly reversed this inhibitory effect, whether given preoperatively or only postoperatively.

Effects of chronic corticosteroids and vitamin a on the healing of intestinal anastomoses

Glucocorticoids exert a deleterious effect on the wound healing process, which has been suggested to result from the anti-inflammatory action of these steroids. In addition, recent studies have demonstrated that glucocorticoids regulate the expression of various genes at the wound site which are likely to encode key players in the wound repair process. Using a murine full-thickness excisional wound healing model, we analyzed the effect of dexamethasone on the expression of various cytokines, growth factors, enzymes, and extracellular matrix molecules in normal and wounded skin. We demonstrate that the proinflammatory cytokines interleukin-1 alpha and -beta, tumor necrosis factor alpha, keratinocyte growth factor, transforming growth factors beta 1, beta 2, and beta 3 and their receptors, platelet-derived growth factors and their receptors, tenascin-C, stromelysin-2, macrophage metalloelastase, and enzymes involved in the generation of nitric oxide are targets of glucocorticoid action in wounded skin. These results indicate that anti-inflammatory steroids inhibit wound repair at least in part by influencing the expression of these key regulatory molecules.

Glucocorticoid-regulated gene expression during cutaneous wound repair.

Involvement of Glucocorticoids in the Development of the Secondary Palate

Fibroblasts are the predominant cells of connective tissue and their integrity is therefore dependent upon factors which influence the metabolism of these cells. The sensitivity of fibroblasts to anti-inflammatory steroids has been shown by the suppression of collagen and mucopolysaccharide synthesis in vivo (Castor and Baker, 1950; Mancini, Stringa, and Canepa, 1960; Houck, Sharma, Patel, and Gladner, 1968) and in vitro (Castor, 1965), and the inhibition of cell growth in vitro (Grossfeld, 1959; Wellings and Moon, 1961; Berliner and Ruhmann, 1967). During prolonged therapy with anti-inflammatory steroids the inhibition described at a cellular level in vitro is reflected in vivo by an increased susceptibility to skin bruising (West, 1961) and by a decrease in skin thickness (Grahame, 1969). At the site of 'steroid bruising' there is a loss and disorganization of dermal collagen (Scarborough and Shuster, 1960). In order to study the mode of action of antiinflammatory steroids on skin, an in vitro fibroblast culture system has been used, and in this paper the effects of two anti-inflammatory steroids (prednisolone and cortisol) on fibroblast growth and metabolism will be described.

https://ard.bmj.com/content/annrheumdis/33/5/437.full.pdf

Effects of steroid hormones on human fibroblasts in vitro. I. Glucocorticoid action on cell growth and collagen synthesis.

Inhibition of dermal activity by cortisol in culture was partially reversed by two naturally occurring androgens, testosterone and dihydrotestosterone. ACTH and the androgen precursor dehydroepiandrosterone sulphate showed not such antagonistic effect. These results suggest that increased production of adrenal androgens during ACTH therapy may account for the relative absnece of 'skin-thinning' and 'steroid-bruising' which are common side-effects of corticosteroid therapy.

https://ard.bmj.com/content/annrheumdis/35/2/148.full.pdf

W Harvey

Papers

Effects of steroid hormones on human fibroblasts in vitro. I. Glucocorticoid action on cell growth and collagen synthesis.

Effects of steriod hormones on human fibroblasts in vitro. II. Antagonism by androgens of cortisol-induced inhibition.

In vitro Effects of D(—)penicillamine on Collagen Synthesis by Human Fibroblasts