Pharmacological analysis of signal transduction pathways required for mycobacterium tuberculosis-induced iL-8 and MCP-1 production in human peripheral monocytes

Anna M. Fietta, Monica Morosini, Federica Meloni, Alessia Marone Bianco, Ernesto Pozzi

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Signalling cascades involved in chemokine production by human phagocytes following infection with Mycobacterium tuberculosis are still not defined. We used specific pharmacologic inhibitors to identify the signalling molecules which lead to interleukin (IL)-8 and MCP-1 production in human monocytes in response to M. tuberculosis infection. Inhibition of extracellular signal-regulated (ERK) or p38 mitogen-activated protein kinase by PD 98059 and SB 203580 respectively, significantly affected chemokine production. However, only the presence of both inhibitors completely blocked the release. A down-regulation of chemokine secretion was found in presence of inhibitors of protein kinase (PK)C and phospholipase C. Moreover, production depended on transcription activation via the nuclear factor-kappa B (NF-κB), as demonstrated by treatment with actinomycin D and caffeic acid phenethyl ester. In addition, activation of PKA and the phosphoinoside 3-kinase (PI-3k)/p70 ribosomal S6 kinase cascade was required to have maximal MCP-1 but not IL-8 production. In conclusion, this study provides evidence that multiple signal transduction pathways are involved in M. tuberculosis-induced chemokine secretion by human monocytes. Moreover, for the first time this report indicates that inhibitors of some signalling molecules are able to dissociate IL-8 from MCP-1 secretion. Differences in the regulatory pathways of chemokine production can potentially be exploited therapeutically.

Original languageEnglish
Pages (from-to)242-249
Number of pages8
JournalCytokine
Volume19
Issue number5
DOIs
Publication statusPublished - 2002

Fingerprint

Signal transduction
Mycobacterium tuberculosis
Chemokines
Monocytes
Signal Transduction
Pharmacology
Interleukin-8
70-kDa Ribosomal Protein S6 Kinases
Chemical activation
Mycobacterium Infections
NF-kappa B
Ribosomal Protein S6 Kinases
Dactinomycin
Type C Phospholipases
p38 Mitogen-Activated Protein Kinases
Phagocytes
Molecules
Protein Kinase C
Transcriptional Activation
Transcription

Keywords

  • Human monocytes/IL-8/MCP-1/M
  • Tuberculosis/signalling pathways

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Immunology
  • Immunology and Allergy

Cite this

Pharmacological analysis of signal transduction pathways required for mycobacterium tuberculosis-induced iL-8 and MCP-1 production in human peripheral monocytes. / Fietta, Anna M.; Morosini, Monica; Meloni, Federica; Bianco, Alessia Marone; Pozzi, Ernesto.

In: Cytokine, Vol. 19, No. 5, 2002, p. 242-249.

Research output: Contribution to journalArticle

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