Aryl hydrocarbon receptor negatively regulates LPS-induced IL-6 production through suppression of histamine production in macrophages

Kazuya Masuda, Akihiro Kimura, Hamza Hanieh, Nam Trung Nguyen, Taisuke Nakahama, Ichino Chinen, Yuichi Otoyo, Tomotaka Murotani, Atsushi Yamatodani, Tadamitsu Kishimoto

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Macrophages play a pivotal role in innate immune responses to pathogens via toll-like receptors. We previously demonstrated that aryl hydrocarbon receptor (Ahr) in combination with signal transducer and activator of transcription 1 (Stat1) negatively regulates pro-inflammatory cytokine production by inhibiting nuclear factor-kB activation in macrophages after LPS stimulation. Here, we show that Ahr also negatively regulates production of the pro-inflammatory cytokine IL-6 by suppressing histamine production in macrophages stimulated by LPS. We found that Ahr-Sp1 complex, independent of Stat1, represses histidine decarboxylase expression by inhibiting LPS-induced Sp1 phosphorylation on Ser residues in macrophages; this leads to suppression of histamine production. Moreover, we found that loratadine and chlorpromazine, histamine 1 receptor (H1R) antagonists, more effectively impair the production of LPS-induced IL-6 than that of other inflammatory cytokines in Ahr 1/1 macrophages. Collectively, these results demonstrate that Ahr negatively regulates IL-6 production via H1R signaling through the suppression of histamine production in macrophages following LPS stimulation.

Original languageEnglish
Pages (from-to)637-645
Number of pages9
JournalInternational Immunology
Volume23
Issue number10
DOIs
Publication statusPublished - 2011 Oct

Fingerprint

Aryl Hydrocarbon Receptors
Histamine
Interleukin-6
Macrophages
STAT1 Transcription Factor
Histamine Receptors
Cytokines
Loratadine
Histidine Decarboxylase
Macrophage Activation
Toll-Like Receptors
Chlorpromazine
Innate Immunity
Phosphorylation

Keywords

  • Aryl hydrocarbon receptor
  • Histamine
  • Histidine decarboxylase
  • Lipopolysaccharide
  • Sp1

ASJC Scopus subject areas

  • Immunology

Cite this

Aryl hydrocarbon receptor negatively regulates LPS-induced IL-6 production through suppression of histamine production in macrophages. / Masuda, Kazuya; Kimura, Akihiro; Hanieh, Hamza; Nguyen, Nam Trung; Nakahama, Taisuke; Chinen, Ichino; Otoyo, Yuichi; Murotani, Tomotaka; Yamatodani, Atsushi; Kishimoto, Tadamitsu.

In: International Immunology, Vol. 23, No. 10, 10.2011, p. 637-645.

Research output: Contribution to journalArticle

Masuda, K, Kimura, A, Hanieh, H, Nguyen, NT, Nakahama, T, Chinen, I, Otoyo, Y, Murotani, T, Yamatodani, A & Kishimoto, T 2011, 'Aryl hydrocarbon receptor negatively regulates LPS-induced IL-6 production through suppression of histamine production in macrophages', International Immunology, vol. 23, no. 10, pp. 637-645. https://doi.org/10.1093/intimm/dxr072
Masuda, Kazuya ; Kimura, Akihiro ; Hanieh, Hamza ; Nguyen, Nam Trung ; Nakahama, Taisuke ; Chinen, Ichino ; Otoyo, Yuichi ; Murotani, Tomotaka ; Yamatodani, Atsushi ; Kishimoto, Tadamitsu. / Aryl hydrocarbon receptor negatively regulates LPS-induced IL-6 production through suppression of histamine production in macrophages. In: International Immunology. 2011 ; Vol. 23, No. 10. pp. 637-645.
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