Interleukin-10 (IL-10) selectively enhances CIS3/SOCS3 mrna expression in human neutrophils: Evidence for an IL-10-induced pathway that is independent of STAT protein activation

Marco A. Cassatella, Sara Gasperini, Chiara Bovolenta, Federica Calzetti, Marieke Vollebregt, Patrizia Scapini, Martina Marchi, Ritsu Suzuki, Asuka Suzuki, Akihiko Yoshimura

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176 Citations (Scopus)

Abstract

We have recently shown that, in human neutrophils, interleukin-10 (IL- 10) fails to induce specific DNA-binding activities to the gamma-interferon response region (GRR), a regulatory element located in the FcγRI gene promoter, which is required for transcriptional activation by IL-10 and interferon γ (IFNγ) in monocytic cells, in this study, we report that IL-10 is also unable to induce the binding of STAT1 or STAT3 to the serum-inducible element (hSIE/m67), despite the fact that both proteins are expressed in neutrophils. Whereas IFNγ and granulocyte colony-stimulating factor (G-CSF) are efficient inducers of STAT1 and STAT3 tyrosine phosphorylation in polymorphonuclear neutrophils (PMN), IL-10 fails to trigger STAT1 and STAT3 tyrosine and serine phosphorylation, therefore explaining its inability to induce the FcγRI expression in these cells. By contrast, we demonstrate that IL-10 alone represents an efficient stimulus of CIS3/SOCS3 mRNA expression in neutrophils. CIS3/SOCS3 belongs to the recently cloned cytokine-inducible SH2-containing protein (CIS) gene family (which also includes CIS1, CIS2, CIS4, CIS5, and JAB) that is believed to be, at least in part, under the control of STAT transcription factors and whose products are potential modulators of cytokine signaling. Moreover, IL-10 synergizes with lipopolysaccharide (LPS) in upregulating CLS3/SOCS3 mRNA expression in PMN through a mechanism that involves mRNA stabilization. In contrast to CLS3/SOCS3, mRNA transcripts encoding other family members are unaffected by IL-10 in neutrophils. Finally, transfection of CLS3/SOCS3 in murine M1 myeloid cells suppresses LPS-induced growth arrest, macrophage-like differentiation, and nitric oxide synthesis, but not IL-6 mRNA expression. Collectively, our data suggest that, in neutrophils, the activation of STAT1 and STAT3 phosphorylation is neither required for CLS3/SOCS3 induction by IL- 10 nor involved in the regulatory effects of IL-10 on cytokine production.

Original languageEnglish
Pages (from-to)2880-2889
Number of pages10
JournalBlood
Volume94
Issue number8
Publication statusPublished - 1999 Oct 15
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Cassatella, M. A., Gasperini, S., Bovolenta, C., Calzetti, F., Vollebregt, M., Scapini, P., Marchi, M., Suzuki, R., Suzuki, A., & Yoshimura, A. (1999). Interleukin-10 (IL-10) selectively enhances CIS3/SOCS3 mrna expression in human neutrophils: Evidence for an IL-10-induced pathway that is independent of STAT protein activation. Blood, 94(8), 2880-2889.