Interleukin-1<i>β</i> prevents the stimulatory effect of transforming growth factor-<i>β</i> on collagen gene expression in human skin fibroblasts

Heino, Jyrki; Heinonen, Toni

doi:10.1042/bj2710827

Cited by 32 publications

(18 citation statements)

References 47 publications

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“…Conflicting data exists regarding the direct effect of IL1β on fibroblasts with respect to collagen expression/synthesis. Elevated levels of collagen expression/synthesis have been reported [29], [30], [31], but also opposite data [22], [26], [27], or no changes at all have been published [32], [33], [34]. We are not aware of studies regarding the effects of IL1β on the differentiation of fibroblasts to myofibroblasts, although a number of studies show that IL1β is able to induce epithelial to mesenchymal transition (EMT) and endothial to mesenchymal transition (EndoMT), i.e.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-1β Attenuates Myofibroblast Formation and Extracellular Matrix Production in Dermal and Lung Fibroblasts Exposed to Transforming Growth Factor-β1

2014

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One of the most potent pro-fibrotic cytokines is transforming growth factor (TGFβ). TGFβ is involved in the activation of fibroblasts into myofibroblasts, resulting in the hallmark of fibrosis: the pathological accumulation of collagen. Interleukin-1β (IL1β) can influence the severity of fibrosis, however much less is known about the direct effects on fibroblasts. Using lung and dermal fibroblasts, we have investigated the effects of IL1β, TGFβ1, and IL1β in combination with TGFβ1 on myofibroblast formation, collagen synthesis and collagen modification (including prolyl hydroxylase, lysyl hydroxylase and lysyl oxidase), and matrix metalloproteinases (MMPs). We found that IL1β alone has no obvious pro-fibrotic effect on fibroblasts. However, IL1β is able to inhibit the TGFβ1-induced myofibroblast formation as well as collagen synthesis. Glioma-associated oncogene homolog 1 (GLI1), the Hedgehog transcription factor that is involved in the transformation of fibroblasts into myofibroblasts is upregulated by TGFβ1. The addition of IL1β reduced the expression of GLI1 and thereby also indirectly inhibits myofibroblast formation. Other potentially anti-fibrotic effects of IL1β that were observed are the increased levels of MMP1, −2, −9 and −14 produced by fibroblasts exposed to TGFβ1/IL1β in comparison with fibroblasts exposed to TGFβ1 alone. In addition, IL1β decreased the TGFβ1-induced upregulation of lysyl oxidase, an enzyme involved in collagen cross-linking. Furthermore, we found that lung and dermal fibroblasts do not always behave identically towards IL1β. Suppression of COL1A1 by IL1β in the presence of TGFβ1 is more pronounced in lung fibroblasts compared to dermal fibroblasts, whereas a higher upregulation of MMP1 is seen in dermal fibroblasts. The role of IL1β in fibrosis should be reconsidered, and the differences in phenotypical properties of fibroblasts derived from different organs should be taken into account in future anti-fibrotic treatment regimes.

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Section: Introductionmentioning

confidence: 99%

Interleukin-1β Attenuates Myofibroblast Formation and Extracellular Matrix Production in Dermal and Lung Fibroblasts Exposed to Transforming Growth Factor-β1

2014

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“…Moreover, because ofour interest in defining the roles ofTGF-(3 in acute and chronic cardiac injury, we have examined whether exogenous TGF-# might have direct effects on myocyte function. Since mediators of acute and chronic cardiac damage, such as IL-1, have been shown to have suppressive effects on myocyte function (10), we also investigated whether TGF-,B might antagonize these effects of IL-1, analogous to its ability to oppose many of the actions of IL-on other cell types (11)(12)(13)(14). We have used cultures of neonatal rat cardiac myocytes which beat spontaneously as a measure of myocyte function, and in this system, show that TGF-,3 plays an intrinsic role in stabilizing their beating rate in serum-free culture and that it is protective against the suppressive effects of IL-I on the contractility of myocytes.…”

Section: Introductionmentioning

confidence: 99%

Role of transforming growth factor-beta in maintenance of function of cultured neonatal cardiac myocytes. Autocrine action and reversal of damaging effects of interleukin-1.

Roberts¹,

Roche²,

Winokur³

et al. 1992

J. Clin. Invest.

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The three isoforms of transforming growth factor-,8 have previously been implicated in embryonic development of the heart as well as in repair of myocardial damage after ischemia/reperfusion injury. TGF-ft1 has also been localized intracellularly to both mitochondria and contractile filaments of cardiac myocytes, although its role in these structures has not been defined. We now report that exogenous TGF-,6 stabilizes the beating rate of neonatal rat cardiac myocytes cultured on fibroblast matrix, and sustains their spontaneous rhythmic beating in serum-free medium. Moreover, using blocking antibodies to TGF-j3, we show that endogenous TGF-ft secreted by these myocytes acts in an autocrine fashion to maintain their beating rate. In contrast, IL-1,6, an inflammatory mediator secreted by immune cells during myocardial injury, inhibits the beating of cardiac myocytes, and TGF-ft can overcome this inhibition. The antagonistic effects of TGF-,# and IL-1 were not observed when the myocytes were cultured on gelatin, as compared to native fibroblast matrix. The data indicate that TGF-,8 is an important regulator of contractile function of the heart and have significant implications for understanding cardiac physiology in health and disease. (J. Clin. Invest. 1992.90:2056-2062.

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“…Together with our results on the effect of PDGF on human skin fibroblasts, this suggests that the liver fat-storing cell and skin fibroblast react in a similar fashion (ie., increased DNA synthesis and increased proliferation), further suggesting that the human skin fibroblast is an adequate cell type to study the effect of fibroproliferative cytokines. Human skin fibroblasts have also been used extensively to study collagen gene expression (26).…”

Section: Discussionmentioning

confidence: 99%

Fibroproliferation in liver disease: Role of monocyte factors

Peterson

Isbrucker

1992

Hepatology

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Fibroproliferation was measured as the uptake of [3H]thymidine into fibroblasts. Human fibroblasts were incubated with 200 microliters monocyte-conditioned medium, the 0.22 microns filtrate from cultured monocytes, in Dulbecco's modified Eagle medium supplemented with controlled process serum replacement 2, a fetal calf serum substitute with low mitogenic activity. Increasing the numbers of fibroblasts resulted in a parallel increase in thymidine uptake to a maximal level. Fibroblasts (2 x 10(3] were plated into microwell plates and incubated with monocyte-conditioned medium for 72 hr. At 16 hr before harvest, 1 muCi [3H]thymidine was added. Cells were harvested with phosphate-buffered saline and washed, and the filters were counted. Fibroblasts incubated with Dulbecco's modified Eagle medium and controlled process serum replacement 2 showed minimal thymidine uptake. Fibroblasts incubated with Dulbecco's modified Eagle medium plus monocyte-conditioned medium from monocytes stimulated with 10 micrograms/ml lipopolysaccharides showed a sixfold increase in thymidine uptake over fibroblasts in Dulbecco's modified Eagle medium and controlled process serum replacement 2 alone. Fibroblasts incubated with Dulbecco's modified Eagle medium plus monocyte-conditioned medium from monocytes of patients with liver disease (n = 20) showed a 10-fold elevation in thymidine uptake compared with Dulbecco's modified Eagle medium and controlled process serum replacement 2. Results indicated that preincubation of monocyte-conditioned medium with either anti-interleukin-1 beta (12.5 half-maximal units, 4 degrees C, 16 hr) or catalase (1,870 IU, 25 degrees C, 1 hr) did not alter the fibroproliferative activity of the monocyte-conditioned medium, suggesting that neither interleukin-1 beta nor activated oxygen intermediates were involved in fibroproliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

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Interleukin-1β prevents the stimulatory effect of transforming growth factor-β on collagen gene expression in human skin fibroblasts

Cited by 32 publications

References 47 publications

Interleukin-1β Attenuates Myofibroblast Formation and Extracellular Matrix Production in Dermal and Lung Fibroblasts Exposed to Transforming Growth Factor-β1

Interleukin-1β Attenuates Myofibroblast Formation and Extracellular Matrix Production in Dermal and Lung Fibroblasts Exposed to Transforming Growth Factor-β1

Role of transforming growth factor-beta in maintenance of function of cultured neonatal cardiac myocytes. Autocrine action and reversal of damaging effects of interleukin-1.

Fibroproliferation in liver disease: Role of monocyte factors

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