Effects of cyclosporin A on cell proliferation and collagen production by human skin fibroblasts

Ono, Masashi; Hatamochi, Atsushi; Arakawa, Masami; Ueki, Hiroaki

doi:10.1016/0923-1811(91)90051-x

Cited by 19 publications

(17 citation statements)

References 36 publications

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“…Nickoloff et al (1988) have reported that CyA suppresses fibroblast proliferation. Ono et al (1991) have shown that CyA inhibits fibroblast proliferation, but not the production of collagenous protein by fibroblasts. Lohi et al (1994) have demonstrated that CyA enhances MMP-1 mRNA expression by fibroblasts when they are stimulated with phorbol 12-myristate 13-acetate, IL-1β, tumor necrosis factor α, or calcium ionophore A23187.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 counteracts effects of cyclosporin A on extracellular matrix metabolism by human dermal fibroblasts

et al. 2008

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Although the actions of cyclosporin (CyA) on keratinocyte are well established, little is known about its effects on dermal fibroblasts. Interleukin-6 (IL-6) is one of the inflammatory cytokines playing a pivotal role in certain skin diseases such as psoriasis. The aim of this study has been to determine whether CyA modifies the metabolism of extracellular matrix (ECM) by human fibroblasts in vitro. CyA altered the morphology of fibroblasts in the collagen matrix. Fibroblast proliferation was suppressed by CyA at 100 and 10 ng/ml. The production of type I collagen and tissue inhibitor of metalloproteinase 1 was also suppressed by CyA at 1000 ng/ml, and co-stimulation with IL-6 enhanced decreased production at 1000 and 100 ng/ml CyA. The production of matrix metalloproteinase 1 (MMP-1) was also suppressed by CyA in a dose-dependent manner. In contrast, the decreased production of MMP-1 was restored at 0.1-100 ng/ml CyA in the presence of IL-6. Regardless of the presence or absence of IL-6, the production of MMP-2 decreased at 1000 and 100 ng/ml, whereas the production of MMP-9 was unchanged. The production of transforming growth factor-beta decreased at 100 ng/ml CyA. This study thus indicates that CyA influences ECM metabolism and the proliferation of human dermal fibroblasts, and that the effects of CyA are modulated by IL-6. CyA might also, in part, improve psoriatic skin by regulating the remodeling of ECM and by its action on immunocompetent cells.

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Section: Discussionmentioning

confidence: 99%

Interleukin-6 counteracts effects of cyclosporin A on extracellular matrix metabolism by human dermal fibroblasts

et al. 2008

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“…Our model enables the detection of the antifibrotic effects of compounds with good reliability for effects as weak as 0.7 of 2 −ΔΔCT , which is therefore wholly sufficient regarding the effects of known activators or inhibitors of fibrogenesis, such as TGF-β or CsA 15,16,29,30 or of a drug with a proven antifibrotic effect such as PFD. 3,18 Indeed, PFD was recently used for 2 years in 28 patients with chronic hepatitis C and was shown to improve inflammation, fibrosis and steatosis; 31 furthermore, it was well tolerated at the dose used during the study (1200 mg/day), and none of the patients dropped out of the study because of the adverse effects of treatment.…”

Section: Discussionmentioning

confidence: 99%

Development of an in vitro model to test antifibrotic drugs on primary human liver myofibroblasts

Aoudjehane¹,

Boëlle²,

Bisch³

et al. 2016

Laboratory Investigation

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We have developed a culture model to assess antifibrotic drugs using normal human liver myofibroblasts (HLMFs) obtained from 31 subjects. Activation was evaluated in terms of α-smooth muscle actin (α-SMA) and collagen 1 (Coll1) expression using RT-PCR, and proliferation as the uptake of 5-ethynil-2′-deoxyuridine. Under analysis of variance, between-subject differences accounted for 70% of all variability and inter-experiment differences for 30%. The sensitivity of the model was determined by quantifying the effects in terms of relative expression, which were 0.74 ± 0.03 for cyclosporine A (CsA) and 2.4 ± 0.10 for transforming growth factor-beta (TGF-β) (Po0.0001 vs no treatment) for α-SMA expression. Inter-subject variations in α-SMA and Coll1 expression enabled the classification of subjects as potentially low or high fibrosers. Finally, we observed that pirfenidone (which has beneficial effects in vivo) significantly reduced the expressions of α-SMA and Coll1, whereas the angiotensin-converting enzyme inhibitor losartan (which has no effect in vivo) had no significant effect. Our model may thus detect the antifibrotic properties of drugs. Antifibrotic drugs with promising clinical relevance could possibly be selected using a bank of HLMFs from high fibrosers.

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“…Although it is not yet being used routinely for ophthalmic purposes, cyc A has also been found effective in humans as a wound-healing retardant [13,22,26,30]. It is suggested that by interfering with the complicated network of interactions between connective tissue and the immune system by down-regulation of the inflammatory phase via modulation of cytokines, cyc A may delay tissue repair [23].…”

Section: Discussionmentioning

confidence: 99%

“…It is suggested that cyc A may inhibit the proliferation of fibroblasts, but not their synthesis of collagenous and non-collagenous proteins at therapeutic concentrations [22]. Its role in wound healing modulation is under investigation [20].…”

Section: Introductionmentioning

confidence: 99%

Ciliary body toxicity of cyclosporin A and octreotide acetate in rabbit eyes: a comparison with mitomycin C and 5-fluorouracil

Akyol

Demır

Çobanoğlu

et al. 2003

Graefe's Arch Clin Exp Ophthalmol

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Effects of cyclosporin A on cell proliferation and collagen production by human skin fibroblasts

Cited by 19 publications

References 36 publications

Interleukin-6 counteracts effects of cyclosporin A on extracellular matrix metabolism by human dermal fibroblasts

Interleukin-6 counteracts effects of cyclosporin A on extracellular matrix metabolism by human dermal fibroblasts

Development of an in vitro model to test antifibrotic drugs on primary human liver myofibroblasts

Ciliary body toxicity of cyclosporin A and octreotide acetate in rabbit eyes: a comparison with mitomycin C and 5-fluorouracil

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