Novel Regulatory Mechanisms of CD40-Induced Prostanoid Synthesis by IL-4 and IL-10 in Human Monocytes

Yasushi Inoue, Takeshi Otsuka, Hiroaki Niiro, Shuji Nagano, Yojirou Arinobu, Eiichi Ogami, Mitsuteru Akahoshi, Katsuhisa Miyake, Ichiro Ninomiya, Sakiko Shimizu, Hitoshi Nakashima, Mine Harada

研究成果: ジャーナルへの寄稿記事

28 引用 (Scopus)

抄録

Interleukins IL-4 and IL-10 are considered to be central regulators for the limitation and eventual termination of inflammatory responses in vivo, based on their potent anti-inflammatory effects toward LPS-stimulated monocytes/macrophages and neutrophils. However, their role in T cell-dependent inflammatory responses has not been fully elucidated. In this study, we investigated the effects of both cytokines on the production of PGE 2, a key molecule of various inflammatory conditions, in CD40-stimulated human peripheral blood monocytes. CD40 ligation of monocytes induced the synthesis of a significant amount of PGE2 via inducible expression of the cyclooxygenase (COX)-2 gene. Both IL-10 and IL-4 significantly inhibited PGE2 production and COX-2 expression in CD40-stimulated monocytes. Using specific inhibitors for extracellular signal-related kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), we found that both kinase pathways are involved in CD40-induced COX-2 expression. CD40 ligation also resulted in the activation of NF-κB Additional experiments exhibited that CD40 clearly induced the activation of the upstream kinases MAPK/ERK kinase 1/2, MAPK kinase 3/6, and I-κB in monocytes. IL-10 significantly inhibited CD40-induced activation of the ERK, p38 MAPK, and NF-κB pathways; however, inhibition by IL-4 was limited to the ERK pathway in monocytes. Neither IL-10 nor IL-4 affected the recruitment of TNFR-associated factors 2 and 3 to CD40 in monocytes. Collectively, IL-10 and IL-4 use novel regulatory mechanisms for CD40-induced prostanoid synthesis in monocytes, thus suggesting a potential role for these cytokines in regulating T cell-induced inflammatory responses, including autoimmune diseases.

元の言語英語
ページ(範囲)2147-2154
ページ数8
ジャーナルJournal of Immunology
172
発行部数4
DOI
出版物ステータス出版済み - 2 15 2004

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Interleukin-4
Interleukin-10
Prostaglandins
Monocytes
Phosphotransferases
Cyclooxygenase 2
p38 Mitogen-Activated Protein Kinases
Dinoprostone
Ligation
MAP Kinase Kinase 6
MAP Kinase Kinase 3
Cytokines
T-Lymphocytes
Proto-Oncogene Proteins c-akt
Prostaglandins E
Mitogen-Activated Protein Kinases
Autoimmune Diseases
Neutrophils
Anti-Inflammatory Agents
Macrophages

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

これを引用

Novel Regulatory Mechanisms of CD40-Induced Prostanoid Synthesis by IL-4 and IL-10 in Human Monocytes. / Inoue, Yasushi; Otsuka, Takeshi; Niiro, Hiroaki; Nagano, Shuji; Arinobu, Yojirou; Ogami, Eiichi; Akahoshi, Mitsuteru; Miyake, Katsuhisa; Ninomiya, Ichiro; Shimizu, Sakiko; Nakashima, Hitoshi; Harada, Mine.

:: Journal of Immunology, 巻 172, 番号 4, 15.02.2004, p. 2147-2154.

研究成果: ジャーナルへの寄稿記事

Inoue, Y, Otsuka, T, Niiro, H, Nagano, S, Arinobu, Y, Ogami, E, Akahoshi, M, Miyake, K, Ninomiya, I, Shimizu, S, Nakashima, H & Harada, M 2004, 'Novel Regulatory Mechanisms of CD40-Induced Prostanoid Synthesis by IL-4 and IL-10 in Human Monocytes', Journal of Immunology, 巻. 172, 番号 4, pp. 2147-2154. https://doi.org/10.4049/jimmunol.172.4.2147
Inoue, Yasushi ; Otsuka, Takeshi ; Niiro, Hiroaki ; Nagano, Shuji ; Arinobu, Yojirou ; Ogami, Eiichi ; Akahoshi, Mitsuteru ; Miyake, Katsuhisa ; Ninomiya, Ichiro ; Shimizu, Sakiko ; Nakashima, Hitoshi ; Harada, Mine. / Novel Regulatory Mechanisms of CD40-Induced Prostanoid Synthesis by IL-4 and IL-10 in Human Monocytes. :: Journal of Immunology. 2004 ; 巻 172, 番号 4. pp. 2147-2154.
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abstract = "Interleukins IL-4 and IL-10 are considered to be central regulators for the limitation and eventual termination of inflammatory responses in vivo, based on their potent anti-inflammatory effects toward LPS-stimulated monocytes/macrophages and neutrophils. However, their role in T cell-dependent inflammatory responses has not been fully elucidated. In this study, we investigated the effects of both cytokines on the production of PGE 2, a key molecule of various inflammatory conditions, in CD40-stimulated human peripheral blood monocytes. CD40 ligation of monocytes induced the synthesis of a significant amount of PGE2 via inducible expression of the cyclooxygenase (COX)-2 gene. Both IL-10 and IL-4 significantly inhibited PGE2 production and COX-2 expression in CD40-stimulated monocytes. Using specific inhibitors for extracellular signal-related kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), we found that both kinase pathways are involved in CD40-induced COX-2 expression. CD40 ligation also resulted in the activation of NF-κB Additional experiments exhibited that CD40 clearly induced the activation of the upstream kinases MAPK/ERK kinase 1/2, MAPK kinase 3/6, and I-κB in monocytes. IL-10 significantly inhibited CD40-induced activation of the ERK, p38 MAPK, and NF-κB pathways; however, inhibition by IL-4 was limited to the ERK pathway in monocytes. Neither IL-10 nor IL-4 affected the recruitment of TNFR-associated factors 2 and 3 to CD40 in monocytes. Collectively, IL-10 and IL-4 use novel regulatory mechanisms for CD40-induced prostanoid synthesis in monocytes, thus suggesting a potential role for these cytokines in regulating T cell-induced inflammatory responses, including autoimmune diseases.",
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AU - Otsuka, Takeshi

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AU - Nagano, Shuji

AU - Arinobu, Yojirou

AU - Ogami, Eiichi

AU - Akahoshi, Mitsuteru

AU - Miyake, Katsuhisa

AU - Ninomiya, Ichiro

AU - Shimizu, Sakiko

AU - Nakashima, Hitoshi

AU - Harada, Mine

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AB - Interleukins IL-4 and IL-10 are considered to be central regulators for the limitation and eventual termination of inflammatory responses in vivo, based on their potent anti-inflammatory effects toward LPS-stimulated monocytes/macrophages and neutrophils. However, their role in T cell-dependent inflammatory responses has not been fully elucidated. In this study, we investigated the effects of both cytokines on the production of PGE 2, a key molecule of various inflammatory conditions, in CD40-stimulated human peripheral blood monocytes. CD40 ligation of monocytes induced the synthesis of a significant amount of PGE2 via inducible expression of the cyclooxygenase (COX)-2 gene. Both IL-10 and IL-4 significantly inhibited PGE2 production and COX-2 expression in CD40-stimulated monocytes. Using specific inhibitors for extracellular signal-related kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), we found that both kinase pathways are involved in CD40-induced COX-2 expression. CD40 ligation also resulted in the activation of NF-κB Additional experiments exhibited that CD40 clearly induced the activation of the upstream kinases MAPK/ERK kinase 1/2, MAPK kinase 3/6, and I-κB in monocytes. IL-10 significantly inhibited CD40-induced activation of the ERK, p38 MAPK, and NF-κB pathways; however, inhibition by IL-4 was limited to the ERK pathway in monocytes. Neither IL-10 nor IL-4 affected the recruitment of TNFR-associated factors 2 and 3 to CD40 in monocytes. Collectively, IL-10 and IL-4 use novel regulatory mechanisms for CD40-induced prostanoid synthesis in monocytes, thus suggesting a potential role for these cytokines in regulating T cell-induced inflammatory responses, including autoimmune diseases.

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