Nitric oxide donors suppress chemokine production by keratinocytes in vitro and in vivo

Maria Laura Giustizieri, Cristina Albanesi, Claudia Scarponi, Ornella De Pità, Giampiero Girolomoni

Research output: Contribution to journalArticle

Abstract

Nitric oxide (NO) is involved in the modulation of inflammatory responses. In psoriatic skin, NO is highly produced by epidermal keratinocytes in response to interferon-γ and tumor necrosis factor-α. In this study, we investigated whether the NO donors, S-nitrosoglutathione (GS-NO) and NOR-1, could regulate chemokine production by human keratinocytes activated with interferon-γ and tumor necrosis factor-a. In addition, we studied the effects of the topical application of a GS-NO ointment on chemokine expression in lesional psoriatic skin. NO donors diminished in a dose-dependent manner and at both mRNA and protein levels the IP-10, RANTES, and MCP-1 expression in keratinocytes cultured from healthy patients and psoriatic patients. In contrast, constitutive and induced interleukin-8 production was unchanged. GS-NO-treated psoriatic skin showed reduction of IP-10, RANTES, and MCP-1, but not interleukin-8 expression by keratinocytes. Moreover, the number of CD14+ and CD3+ cells infiltrating the epidermis and papillary dermis diminished significantly. NO donors also down-regulated ICAM-1 protein expression without affecting mRNA accumulation in vitro, and suppressed keratinocyte ICAM-1 in vivo. Finally, NO donors inhibited nuclear factor-κB and STAT-1, but not AP-1 activities in transiently transfected keratinocytes. These results define NO donors as negative regulators of chemokine production by keratinocytes.

Original languageEnglish
Pages (from-to)1409-1418
Number of pages10
JournalAmerican Journal of Pathology
Volume161
Issue number4
Publication statusPublished - Oct 1 2002

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Nitric Oxide Donors
Keratinocytes
Chemokines
Nitric Oxide
Chemokine CCL5
Intercellular Adhesion Molecule-1
Interleukin-8
Skin
Interferons
Tumor Necrosis Factor-alpha
S-Nitrosoglutathione
Messenger RNA
Transcription Factor AP-1
Dermis
Ointments
In Vitro Techniques
Epidermis
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Nitric oxide donors suppress chemokine production by keratinocytes in vitro and in vivo. / Giustizieri, Maria Laura; Albanesi, Cristina; Scarponi, Claudia; De Pità, Ornella; Girolomoni, Giampiero.

In: American Journal of Pathology, Vol. 161, No. 4, 01.10.2002, p. 1409-1418.

Research output: Contribution to journalArticle

Giustizieri, Maria Laura ; Albanesi, Cristina ; Scarponi, Claudia ; De Pità, Ornella ; Girolomoni, Giampiero. / Nitric oxide donors suppress chemokine production by keratinocytes in vitro and in vivo. In: American Journal of Pathology. 2002 ; Vol. 161, No. 4. pp. 1409-1418.
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