Involvement of MAP kinases in lipopolysaccharide-induced histamine production in RAW 264 cells

Noriyasu Hirasawa1, Masashi Torigoe, Ryohko Ohgawara

  • 1Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan. hirasawa@mail.pharm.tohoku.ac.jp

Life Sciences
|September 19, 2006
PubMed

Insights

Lipopolysaccharide (LPS) triggers histamine production in mouse RAW 264 cells by increasing histidine decarboxylase (HDC) expression. Mitogen-activated protein (MAP) kinases, particularly p44 and JNK, regulate this LPS-induced HDC upregulation at the transcriptional level.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Lipopolysaccharide (LPS) is a potent immune activator.
  • Histamine is a key mediator in inflammatory responses.
  • Mitogen-activated protein (MAP) kinases play crucial roles in cellular signaling pathways.

Purpose of the Study:

  • To investigate the role of MAP kinases in LPS-induced histamine production in RAW 264 cells.
  • To elucidate the signaling pathways involved in regulating histidine decarboxylase (HDC) expression by LPS.

Main Methods:

  • RAW 264 cells were treated with LPS and various MAP kinase inhibitors (U0126, SP600125, SB203580).
  • Histamine levels, HDC mRNA, and 74-kDa HDC protein expression were measured.
  • Phosphorylation of p44/42 MAP kinase, p38 MAP kinase, and c-Jun N-terminal kinase (JNK) was assessed.

Main Results:

  • LPS significantly increased histamine production, HDC mRNA, and 74-kDa HDC protein levels in a dose- and time-dependent manner.
  • LPS induced the phosphorylation of p44/42 MAP kinase, p38 MAP kinase, and JNK.
  • Inhibitors of p44/42 MAP kinase (U0126) and JNK (SP600125) suppressed LPS-induced histamine production and HDC expression.
  • p38 MAP kinase inhibition partially reduced histamine production.

Conclusions:

  • LPS enhances histamine production in RAW 264 cells by upregulating 74-kDa HDC protein expression.
  • MAP kinases, especially p44 MAP kinase and JNK, are critical regulators of LPS-induced HDC expression at the transcriptional level.