5-hydroxytryptophan acts on the mitogen-activated protein kinase extracellular-signal regulated protein kinase pathway to modulate cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW 264.7 cells

Biol Pharm Bull. 2009 Apr;32(4):553-7. doi: 10.1248/bpb.32.553.

Abstract

In this study, we evaluated the effect of 5-hydroxytryptophan on anti-inflammatory and analgesic activity in RAW 264.7 cells. Cells were treated with different concentrations of 5-hydroxytryptophan for either 1 h or for 24 h. The anti-inflammatory effect was then analyzed by enzyme-linked immunosorbent assay (ELISA), Western blotting and reverse transcription polymerase chain reaction (RT-PCR). In addition, the analgesic activity was evaluated by measuring the acetic acid-induced writhing response. We found that 5-hydroxytryptophan significantly reduced the acetic acid-induced writhing response. Moreover we evaluated the effects of 5-hydroxytryptophan on the release of several inflammatory mediators including nitric oxide (NO) and interleukin-6 (IL-6). Our results demonstrated that 5-hydroxytryptophan inhibited the lipopolysaccharide (LPS)-induced expression of NO and IL-6. Furthermore, we found that 5-hydroxytryptophan played a role in LPS induced inducible nitric oxide synthase (iNOS), cyclo oxygenase-2 (COX-2) and extracellular-signal regulated protein kinase (ERK) activation. Taken together, these results indicate that 5-hydroxytryptophan has the potential for use in the treatment of inflammatory disease and as an analgesic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Hydroxytryptophan / pharmacology*
  • Analgesics, Non-Narcotic / pharmacology
  • Animals
  • Blotting, Western
  • Cyclooxygenase 2 / biosynthesis*
  • Enzyme-Linked Immunosorbent Assay
  • Interleukin-6 / biosynthesis
  • Macrophages / drug effects
  • Macrophages / enzymology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mitogen-Activated Protein Kinases / physiology*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / biosynthesis*
  • Pain Measurement / drug effects
  • Phosphorylation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • Tetrazolium Salts
  • Thiazoles

Substances

  • Analgesics, Non-Narcotic
  • Interleukin-6
  • Tetrazolium Salts
  • Thiazoles
  • Nitric Oxide
  • 5-Hydroxytryptophan
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Mitogen-Activated Protein Kinases
  • thiazolyl blue