Post-transcriptional effects of extracellular pH on tumour necrosis factor-α production in RAW 246.7 and J774 A.1 cells

T. A. Heming, D. M. Tuazon, S. K. Davé, A. K. Chopra, J. W. Peterson, A. Bidani

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


The present studies determined the effects of extracellular pH (pHo) on the production of tumour necrosis factor-α (TNF-α) in the macrophage-like cell lines RAW 246.7 and J774 A.1. The cells were activated with lipopolysaccharide (LPS) at pHo 5.5, 6.5 or 7.4. TNF-α gene transcription was monitored by Northern blot analysis. Synthesis of the cytokine was monitored by ELISA measurements of the TNF-α content of cell-conditioned media (extracellularly released TNF-α) and cell lysates (cytosolic TNF-α). The magnitude of the TNF-α response differed markedly between the two cell lines. RAW cells were more responsive to LPS than were J774 cells. However, the effects of pHo on TNF-α production were similar in the two cell lines. TNF-α gene transcription was insensitive to experimental pHo. The pHo had no effect on the abundance of TNF-α mRNA at 2, 4 or 18 h. Nonetheless, synthesis of TNF-α was affected significantly by pHo. The TNF-α contents of cell-conditioned medium and cell lysate at I8h were reduced progressively at lower pHo values. The data indicate that pHo alters TNF-α production in RAW and J774 cells at a post-transcriptional level. These findings suggest that pHo influences the phenotypic responses of macrophages to activating stimuli and modifies the role that macrophages play in inflammatory and immune actions.

Original languageEnglish (US)
Pages (from-to)259-266
Number of pages8
JournalClinical Science
Issue number3
StatePublished - 2001


  • Cytokine
  • Lipopolysaccharide
  • Macrophage

ASJC Scopus subject areas

  • General Medicine


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