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

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

研究成果: ジャーナルへの寄稿記事

88 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)3736-3745
ページ数10
ジャーナルBlood
85
発行部数12
出版物ステータス出版済み - 1 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

これを引用

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

:: Blood, 巻 85, 番号 12, 01.01.1995, p. 3736-3745.

研究成果: ジャーナルへの寄稿記事

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, 巻. 85, 番号 12, pp. 3736-3745.
Niiro, H. ; 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. :: Blood. 1995 ; 巻 85, 番号 12. pp. 3736-3745.
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title = "Inhibition by interleukin-10 of inducible cyclooxygenase expression in lipopolysaccharide-stimulated monocytes: Its underlying mechanism in comparison with interleukin-4",
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.",
author = "H. Niiro and T. Otsuka and T. Tanabe and S. Hara and S. Kuga and Y. Nemoto and Y. Tanaka and H. Nakashima and S. Kitajima and M. Abe and Y. Niho",
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T1 - Inhibition by interleukin-10 of inducible cyclooxygenase expression in lipopolysaccharide-stimulated monocytes

T2 - Its underlying mechanism in comparison with interleukin-4

AU - Niiro, H.

AU - Otsuka, T.

AU - Tanabe, T.

AU - Hara, S.

AU - Kuga, S.

AU - Nemoto, Y.

AU - Tanaka, Y.

AU - Nakashima, H.

AU - Kitajima, S.

AU - Abe, M.

AU - Niho, Y.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - 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.

AB - 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.

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