Interleukin-8 is a Cyclosporin A binding protein

Bang, Holger; Brune, Kay; Nager, Christoph; Feige, Ulrich

doi:10.1007/bf01955157

“…Interestingly, a direct interaction of CsA or its analogues with different cellular proteins, including plasma membrane proteins, has been demonstrated [20][21][22]37,38]. This possibility is not evident, however, from the in vivo data provided in the present study.…”

Section: Discussioncontrasting

confidence: 66%

Lack of effect of clinical doses of cyclosporin A on erythrocyte Na+/K+-ATPase activity

FERRER-MARTÍNEZ¹,

Felipe²,

BARCELÓ³

et al. 1999

Clinical Science

1

0

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Cyclosporin A (CsA) may exert its cytotoxic effects by altering the activity of different plasma membrane transport systems. Although CsA may act at the gene level, it has been also suggested that it can directly alter transport processes at the plasma membrane. To examine this possibility in a physiological context, we determined Na(+)/K(+)-ATPase activity in erythrocytes from two groups of subjects receiving CsA treatment: group I consisted of kidney transplant patients, and group II comprised patients with steroid-resistant idiopathic nephrotic syndrome. Group I patients showed a marked decrease (35%) in the activity of the Na(+)/K(+)-ATPase in erythrocytes immediately after surgery, before the initiation of CsA treatment. The activity remained low 2 days after the introduction of CsA, but had recovered to the original (pre-surgery) value 1 month later. Group II patients showed the same pattern of erythrocyte Na(+)/K(+)-ATPase activity as those in group I. When the blood CsA levels from all patients were plotted against the corresponding erythrocyte Na(+)/K(+)-ATPase transport activity, a significant linear correlation was found. Higher levels of CsA in the blood were correlated significantly with increased Na(+)/K(+)-ATPase activities. The blood sodium concentration was also correlated positively with both erythrocyte Na(+)/K(+)-ATPase activity and blood CsA concentration. Thus CsA treatment is not associated with inhibition of the Na(+)/K(+)-ATPase in erythrocytes.

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“…7,25,26 It has been demonstrated that CsA inhibits lymphocyte chemotaxis 27 and pulmonary recruitment of inflammatory leukocytes 5 and that interleukin-8-a chemokine that recruits and activates neutrophils-is a cyclosporin A binding protein. 28 Furthermore the cyclosporin binding proteins or cyclophilins are chemotactic for eosinophils and neutrophils 29 and their chemotactic activity is inhibited by CsA. 29 Therefore it seems that CsA modulates chemotaxis.…”

Section: Discussionmentioning

confidence: 98%

Effect of cyclosporin A on inflammatory cytokine production by U937 monocyte‐like cells

García

¹

,

Cabo²,

Rodríguez

³

et al. 2000

Mediators of Inflammation

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Cyclosporin A (CsA) is an immunosuppresor drug that has been used in the treatment of several types of inflammatory diseases. In some of them the inhibition of T-lymphocyte activation does not suitably account for the observed beneficial effect, suggesting that CsA could act on other types of cells. The present study was undertaken to determine the effect of CsA on inflammatory cytokine secretion by U937 monocyte cells. Undifferentiated and dimethylsulfoxide (DMSO) differentiated U937 cells were incubated with different concentrations of CsA (200, 20 and 2 ng/mL) in the presence or absence of phorbol-myristate-acetate (PMA). Interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6 and IL-8 levels were measured in supernatants using specific enzyme-linked immunosorbent assays. At the highest concentration used (200 ng/mL) CsA decreased the basal and stimulated secretion of all the inflammatory cytokines studied in both undifferentiated and differentiated cells, with the only exception of PMA-stimulated IL-1 secretion by undifferentiated cells. However, only basal secretion of interleukin-8 in both undifferentiated and DMSO-differentiated U937 cells was significantly reduced by CsA at the highest concentration (200 ng/ mL). At therapeutic concentrations in vivo, CsA exerts a predominant effect on IL-8 secretion by human mononuclear phagocytes.

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“…Interestingly, a direct interaction of CsA or its analogues with different cellular proteins, including plasma membrane proteins, has been demonstrated [20][21][22]37,38]. Interestingly, a direct interaction of CsA or its analogues with different cellular proteins, including plasma membrane proteins, has been demonstrated [20][21][22]37,38].…”

Section: Discussionmentioning

confidence: 99%

Lack of effect of clinical doses of cyclosporin A on erythrocyte Na+/K+-ATPase activity

Ferrer-Martı́nez

¹

,

Felipe

²

,

Barceló

³

et al. 1999

View full text Add to dashboard Cite

Cyclosporin A (CsA) may exert its cytotoxic effects by altering the activity of different plasma membrane transport systems. Although CsA may act at the gene level, it has been also suggested that it can directly alter transport processes at the plasma membrane. To examine this possibility in a physiological context, we determined Na(+)/K(+)-ATPase activity in erythrocytes from two groups of subjects receiving CsA treatment: group I consisted of kidney transplant patients, and group II comprised patients with steroid-resistant idiopathic nephrotic syndrome. Group I patients showed a marked decrease (35%) in the activity of the Na(+)/K(+)-ATPase in erythrocytes immediately after surgery, before the initiation of CsA treatment. The activity remained low 2 days after the introduction of CsA, but had recovered to the original (pre-surgery) value 1 month later. Group II patients showed the same pattern of erythrocyte Na(+)/K(+)-ATPase activity as those in group I. When the blood CsA levels from all patients were plotted against the corresponding erythrocyte Na(+)/K(+)-ATPase transport activity, a significant linear correlation was found. Higher levels of CsA in the blood were correlated significantly with increased Na(+)/K(+)-ATPase activities. The blood sodium concentration was also correlated positively with both erythrocyte Na(+)/K(+)-ATPase activity and blood CsA concentration. Thus CsA treatment is not associated with inhibition of the Na(+)/K(+)-ATPase in erythrocytes.

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Interleukin-8 is a Cyclosporin A binding protein

Cited by 17 publications

References 39 publications

Lack of effect of clinical doses of cyclosporin A on erythrocyte Na+/K+-ATPase activity

Lack of effect of clinical doses of cyclosporin A on erythrocyte Na+/K+-ATPase activity

Effect of cyclosporin A on inflammatory cytokine production by U937 monocyte‐like cells

Lack of effect of clinical doses of cyclosporin A on erythrocyte Na+/K+-ATPase activity

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