Cytokine gene expression in B-cell chronic lymphocytic leukemia: Evidence of constitutive interleukin-8 (IL-8) mRNA expression and secretion of biologically active IL-8 protein

Paola Francia Di Celle, Anna Carbone, Daniela Marchis, Dan Zhou, Silvano Sozzani, Simona Zupo, Massimo Pini, Alberto Mantovani, Robin Foa

Research output: Contribution to journalArticle

Abstract

To extend our knowledge on the cytokines possibly involved in the pathophysiology of B-cell chronic lymphocytic leukemia (B-CLL), the mRNA expression of a panel of 10 cytokines was investigated on purified B-CLL cells using a reverse-transcriptase polymerase chain reaction method. Whereas negative RT-PCR signals were recorded for interleukin-1α (IL-1α), IL-2, IL- 3, IL-4, IL-5, IL-7, tumor necrosis factor β (TNFβ), and granulocyte- macrophage colony-stimulating factor, we detected the expression of IL-1β, IL-6 and TNFα. Furthermore, the constitutive expression of IL-8 mRNA was observed in all 17 B-CLL samples analyzed. mRNA expression was associated with the capacity of the leukemic cells to release IL-8 both constitutively (4.6 ± 8.1 SD ng/mL) and, to a further extent, after stimulation (14.5 ± 19.4 ng/mL). The circulating levels of IL-8 were also evaluated in 12 untreated B-CLL sera samples and the overall mean level was significantly higher (P <.01) than in normal sera. In addition, supernatants of purified B-CLL cells cultured in the presence of 12-O-tetradecanoylphorbol-13-acetate showed chemotactic activity towards neutrophils; this activity was neutralized in the presence of an anti-IL-8 antiserum. The mRNA for IL-8 was absent in five B-cell preparations from hairy cell leukemia cases and in four B-cell lines. Normal tonsil CD5+ B cells showed a low expression of IL-8 mRNA only in two of the nine preparations tested and the overall quantity of IL-8 released by these cells after 3 days' incubation was significantly lower compared with that released by B-CLL cells (0.4 ± 0.3 and 1.6 ± 0.9 ng/mL under basal and stimulated conditions, respectively). These findings point to an involvement of a member of the proinflammatory chemokine super-gene family in human CD5+ B lymphocytes. The different IL-8 behavior observed between B- CLL cells and their normal counterpart is likely to reflect an activation state of the leukemic population.

Original languageEnglish
Pages (from-to)220-228
Number of pages9
JournalBlood
Volume84
Issue number1
Publication statusPublished - Jul 1 1994

ASJC Scopus subject areas

  • Hematology

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