Inhibition by interleukin-10 of inducible cyclooxygenase expression in lipopolysaccharide-stimulated monocytes: Its underlying mechanism in comparison with interleukin-4

Hiroaki Niiro, T. Otsuka, T. Tanabe, S. Hara, S. Kuga, Y. Nemoto, Y. Tanaka, H. Nakashima, S. Kitajima, M. Abe, Y. Niho

Research output: Contribution to journalArticle

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Abstract

Both interleukin-10 (IL-10) and IL-4 inhibited the prostanoid synthesis of lipopolysaccharide (LPS)-stimulated human monocytes, and their inhibition was shown to be based on a common mechanism to suppress the gene expression of inducible cyclooxygenase (COX). COX has been shown to exist in at least two distinct isoforms, designated COX-1 and COX-2, and their gene expressions exhibit different profiles. At both the protein and mRNA levels, the expression of COX-1 was constitutive and was not modulated by treatments with LPS, IL-10, or IL-4. In contrast, the expression of COX-2 was observed only after stimulation with LPS. IL-10 and IL-4 significantly inhibited LPS- induced COX-2 expression. Kinetic studies showed that they inhibited COX-2 mRNA expression within 1 hour after stimulation and that maximal inhibition was consistently observed at 5 hours. Moreover, the addition of cycloheximide (CHX) to LPS-stimulated monocytes resulted in a superinduction of COX-2 mRNA, whereas CHX almost abrogated the abilities of IL-10 and IL-4 to inhibit this gene expression. Experiments with actinomycin D showed that both cytokines accelerated the degradation of COX-2 mRNA. Furthermore, nuclear run-on experiments showed that both cytokines modestly inhibited LPS-induced COX-2 gene transcription. Thus, both cytokines seemed to regulate the COX-related pathway in a similar manner, although their receptor systems did not show any structural similarities. Considering recent findings showing that the drugs that exhibit a selective effect on COX-2 may be more preferable in inflammatory conditions, such biologic activities of IL-10 and IL-4 described above may offer useful tools in controlling inflammatory disorders in the future.

Original languageEnglish
Pages (from-to)3736-3745
Number of pages10
JournalBlood
Volume85
Issue number12
Publication statusPublished - Jan 1 1995

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Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
Interleukin-4
Interleukin-10
Lipopolysaccharides
Monocytes
Gene expression
Cyclooxygenase 1
Messenger RNA
Cycloheximide
Cytokines
Gene Expression
Dactinomycin
Transcription
Prostaglandins
Protein Isoforms
Genes
Experiments
Degradation
Kinetics

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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Inhibition by interleukin-10 of inducible cyclooxygenase expression in lipopolysaccharide-stimulated monocytes : Its underlying mechanism in comparison with interleukin-4. / Niiro, Hiroaki; Otsuka, T.; Tanabe, T.; Hara, S.; Kuga, S.; Nemoto, Y.; Tanaka, Y.; Nakashima, H.; Kitajima, S.; Abe, M.; Niho, Y.

In: Blood, Vol. 85, No. 12, 01.01.1995, p. 3736-3745.

Research output: Contribution to journalArticle

Niiro, H, Otsuka, T, Tanabe, T, Hara, S, Kuga, S, Nemoto, Y, Tanaka, Y, Nakashima, H, Kitajima, S, Abe, M & Niho, Y 1995, 'Inhibition by interleukin-10 of inducible cyclooxygenase expression in lipopolysaccharide-stimulated monocytes: Its underlying mechanism in comparison with interleukin-4', Blood, vol. 85, no. 12, pp. 3736-3745.
Niiro, Hiroaki ; Otsuka, T. ; Tanabe, T. ; Hara, S. ; Kuga, S. ; Nemoto, Y. ; Tanaka, Y. ; Nakashima, H. ; Kitajima, S. ; Abe, M. ; Niho, Y. / Inhibition by interleukin-10 of inducible cyclooxygenase expression in lipopolysaccharide-stimulated monocytes : Its underlying mechanism in comparison with interleukin-4. In: Blood. 1995 ; Vol. 85, No. 12. pp. 3736-3745.
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AU - Tanaka, Y.

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