RESUMEN
A role for the cytokines produced by tissue-infiltrated inflammatory cells (mainly T-lymphocytes and mast cells) in the pathophysiology of fibrosis has been suggested by several groups. Among the products of these cells, interleukin-4 (IL-4) might be one of the factors involved in the initiation of the fibrotic process. We studied the effects of recombinant human IL-4 on human fibroblast monolayer cultures. IL-4 (10 and 100 U/ml) induced a dose-dependent increase of collagen production. Non-collagen protein synthesis was not significantly altered. A concomitant increase of pro-alpha 1(I) collagen mRNAs was observed, showing that IL-4 acts at a pre-translational level.
Asunto(s)
Colágeno/genética , Fibroblastos/metabolismo , Expresión Génica , Interleucina-4/farmacología , Northern Blotting , Células Cultivadas , Colágeno/biosíntesis , Relación Dosis-Respuesta a Droga , Fibrosis , Humanos , Hidroxilación , Interleucina-4/administración & dosificación , Prolina/metabolismo , ARN Mensajero/genéticaRESUMEN
We report the stimulation of elastase activity of human skin fibroblasts by interleukin-1 beta (IL-1). Elastase activity was determined by the hydrolysis of the synthetic substrate succinoyl trialanine paranitroanilide (Suc(Ala3)NA). Recombinant human IL-1 beta induced a concentration-dependent increase in the elastase activity of fibroblasts. The supernatants of keratinocyte cultures that contained IL-1/ETAF showed similar stimulatory activity.
Asunto(s)
Interleucina-1/metabolismo , Elastasa Pancreática/metabolismo , Piel/enzimología , Adulto , Células Cultivadas , Relación Dosis-Respuesta a Droga , Epidermis/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/enzimología , Humanos , Interleucina-1/farmacología , Queratinocitos/metabolismo , Piel/efectos de los fármacosRESUMEN
Interleukin-4 (IL-4) is one of the products of T-lymphocytes and mast cells, inflammatory cells which accumulate in connective tissues at early stages of fibrosis. We tested the effects of IL-4 on human fibroblasts from normal and scleroderma skin seeded in three dimensional collagen lattices ("dermal equivalents"). IL-4 (10 and 100 U/ml) stimulated collagen synthesis in a dose-dependent manner. No significant alteration of lattice retraction and cell proliferation was observed. At the concentration 100 U/ml, Il-4 was approximately twice more efficient on collagen synthesis than Transforming Growth Factor beta (10 ng/ml). IL-4 secretion in connective tissues might be an important factor for the development of fibrotic processes.