Abstract
Lanas A, Haggerty P, Hirschowitz BI. In vitro studies of anti-inflammatory agents and prostaglandin E effects on stimulated normal human fibroblast cultures. Inflammopharmacology. 1994;2:377-387. To study the mechanisms whereby anti-inflammatory agents and prostaglandins may affect wound healing (fibroblast proliferation), we studied normal human fibroblasts growth in short-term, 24 h, culture by13H-thymidine incorporation and longer term 6–14 day growth in cell numbers by the crystal violet method. Therapeutic doses of 5-aminosalicylic acid (5-ASA) but not ibuprofen increase fibroblast proliferation stimulated for 24 h by platelet-derived growth factor (PDGF-AB). Both dexamethasone and prostaglandin-E2 strongly suppressed fibroblast growth but the effects were not additive. PDGF stimulated PGK2 production from fibroblasts and our data suggest that prostaglandins may act as negative Feedback on growth factor mitogenesis. Long-term fibroblast culture was inhibited by ibuprofen but not 5-ASA. We conclude that these effects may explain, at least in part, the clinical actions of these drugs on some pathological conditions and wound healing.
Similar content being viewed by others
References
Hunt TK. The principles of wound healing. In: Halter F, Garner A, Tytgat GNJ, eds. Mechanisms of peptic ulcer healing. Falk Symposium 59. Dordrecht, The Netherlands: Kluwer Academic Publishers 1991:1–12.
Phan SH, McGarry KM, Loeffler KM, Kunkel SL. Regulation of macrophage-derived fibroblast growth factor release by arachidonate metabolites. J Leukocyte Biol. 1987;42:106–13.
Baud L, Perez J, Denis M, Ardaillou R,Modulation of fibroblast proliferation by sulfidopeptide leukotrienes: effect of indomethacin. J Immunol. 1987;138:1190–5.
Wickeremashinghe RG. The role of prostaglandins in the regulation of cell proliferation. Prostaglandins Leukot Essent Fatty Acids. 1988;31:171–9.
De Asua LJ, Clingan D, Rudland PS. Initiation of cell proliferation in cultured mouse fibroblasts by prostaglandin F2 alpha. Proc Natl Acad Sci USA. 1975;72:2724–8.
Durant S, Duval D, Homo-Delarche F. Effect of exogenous prostaglandins and nonsteroidal anti-inflammatory agents on prostaglandin secretion and proliferation of mouse embryo fibroblasts in culture. Prostglandin Leukot Essent Fatty Acids. 1989;38:1–8.
Hori T, Kashiyama S, Hayakawa M et al. Possible role of prostaglandins as negative regulators in growth stimulation by tumor necrosis factor and epidermal growth factor in human fibroblasts. J Cell Physiol. 1989;141:275–80.
De Vos M, Verdeivel H, Schoonjans R, Praet M, Bogaert M, Barbier F. Concentrations of 5-ASA and Ac-5-ASA in human ileocolon in biopsy homogenates after oral 5-ASA preparations. Gut. 1992;33:1338–42.
Korn JH, Halushka PV, Leroy EC. Mononuclear cell modulation of connective tissue function. Supression of fibroblast growth by stimulation of endogenous prostaglandin production. J Clin Invest. 1980;65:543–4.
Nathan CF. Secretory products of macrophages. J Clin Invest. 1987;79:319–26.
Ross R. Platelet-derived growth factor. Lancet. 1989;l:1179–82.
Guglietta A, Nardi RV. PDGF-BB accelerates healing of indomethacin-induced gastric lesions in rats. Gastroenterology. 1992;102:A.
Greenhalgh DG, Sprugel KH, Murray MJ, Ross R. PDGF and FGF stimulate wound healing in the genetically diabetic mouse. Am J Pathol. 1990;136:1235–46.
Lanas A, Hirschowitz BI. Ingestion of aspirin prevents platelet aggregation and impairs release of growth factors — implications for peptic ulcer healing. Scand J Gastroenterol. 1994;24:in press.
Hial V, De Mello MCF, Horakova Z, Beaven MA. Antiproliferative activity of anti-inflammatory drugs in two mammalian cell culture lines. J Pharmacol Exp Ther. 1977;202:446–54.
Bayer B, Kruth HS, Vaughan M, Beaven MA. Arrest of cultured cells in the GI phase of the cell cycle by indomethacin. J Pharmacol Exp Ther. 1979;210:106–11.
Owen NE, Villereal ML. Na influx and cell growth in cultured human fibroblasts. Effect of indomethacin. Exp Cell Res. 1983;143:37–46.
Brooks PM, Day RO. Nonsteroidal antiinflammatory drugs — differences and similarities. N Engl J Med. 1991;324:1716–25.
Sircar JC, Schwender CF, Carethers ME. Inhibition of soybean lipoxygenase by sulfasalazine and 5-aminosalicylic acid: a possible mode of action in ulcerative colitis. Biochem Pharmacol. 1983;32:170–2.
Hirata Y, Uchihashi M, Nakashima H, Fujita T, Matsukura S. Stimulatory effect of epidermal growth factor on prostaglandin E2 production in mouse fibrosarcoma cell line (HSDM1 C1). Horm Met Res. 1985;9:448–50.
Antoniades NH. PDGF: a multifunctional growth factor. Baillieres Clin Endocrinol Metab. 1991;5:595–613.
Eliass JA, Zurier RB, Screiber AD, Leff JA, Daniele RP. Monocyte inhibition of lung fibroblast growth: relationship to fibroblast prostaglandin production and density-defined monocyte subpopulations. J Leukocyte Biol. 1985;37:15–28.
Handler JA, Danilowicz RM, Eling TE. Mitogenic signalling by epidermal growth factor (EGF), but not platelet derived growth factor, requires arachidonic acid metabolism in BALB/c 3T3 cells. Modulation of EGF-dependent c-myc expression by prostaglandins. J Biol Chem. 1990;265:3669–73.
Nakamura A, Yamatani T, Fujita T, Chiba T. Mechanism of inhibitory action of prostaglandins on the growth of human gastric carcinoma cell line KATO III. Gastroenterology. 1991;101:910–8.
Ko SD, Page RC, Narayanan AS. Fibroblast heterogeneity and prostaglandin regulation of subpopulations. Proc Natl Acad Sci USA. 1977;74:3429–32.
Dinarello CA. Biology of interleukin 1. FASEB J. 1988;2:108–15.
Yan XQ, Brady G, Iscove NN. Platelet-derived growth factor (PDGF) activates primitive hematopoietic precursors (pre-CFCmulti) by up-regulating IL-1 in PDGF receptor-expressing macrophages. J Immunol. 1993; 150:2440–8.
Shier WT, Durkin JP. Role of stimulation of arachidonic acid release in the proliferative response of 3T3 mouse fibroblasts to platelet-derived growth factor. J Cell Physiol. 1982;112:171–81.
Ross R, Raines EW, Bowen-Pope DF. The biology of platelet-derived growth factor. Cell. 1986;46:155–69.
Blakeley DM, Corps AN, Brown KD. Bombesin and platelet-derived growth factor stimulate formation of inositol phosphates and Ca mobilization in Swiss 3T3 cells by different mechanisms. Biochem J. 1989;258:177–85.
Robert A, Nezamis JE. Effect of prednisolone on gastric mucus content and on ulcer formation. Proc Soc Exp Biol Med. 1963;114:545–50.
Pierce GL, Mustoe TA, Lingelbach J, Masakowski VR, Gramates P, Deuel TF. Transforming growth factor beta reverses the glucocorticoid-induced wound-healing deficit in rats: possible regulation in macrophages by platelet-derived growth factor. Proc Natl Acad Sci USA. 1989;86:2229–33.
Hase S, Nakazawa S, Tsukamoto S, Segawa K. Effects of prednisolone and human growth factor on angiogenesis in granulation tissue of gastric ulcer induced by acetic acid. Digestion. 1989;42:135–42.
Hirata F. The regulation of lipomodulin, a phospholipase inhibitory protein, in rabbit neutrophils by phosphorylation. J Biol Chem. 1981;256:7730–3.
Pash JM, Bailey JM. Inhibition by corticosteroids of epidermal growth factor-induced recovery of cyclooxygenase after aspirin inactivation. FASEB J. 1988;2:2613–8.
Kawahara RS, Deng ZW, Deuel TF. Glucocorticosteroids inhibit the transcriptional induction of JE, a platelet-derived growth factor-inducible gene. J Biol Chem. 1991;266:13261–6.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lanas, A., Haggerty, P. & Hirschowitz, B.I. In vitro studies of Anti-Inflammatory agents and prostaglandin e2 effects on stimulated normal human fibroblast cultures. Inflammopharmacology 2, 377–387 (1994). https://doi.org/10.1007/BF02678604
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02678604