Vergleich der Signaltransduktion von Interleukin-6 und Interleukin-10 in primären humanen Makrophagen

Different sensitivities of IL-10- and IL-6-induced STAT3 activation towards inhibitory mechanisms in primary human macrophages. Interleukin-10 (IL-10) acts on human macrophages as a more potent anti-inflammatory cytokine than interleukin-6 (IL-6) although both cytokines signal mainly via activation of the transcription factor STAT3. In this study I compared IL-10 and IL-6 signaling in primary human macrophages derived from blood monocytes. Whereas pretreatment of macrophages with PMA or the pro-inflammatory mediators LPS and TNFalpha blocks IL-6-induced STAT3 activation, IL-10-induced activation of STAT3 remains largely unaffected. Although LPS induces the feedback inhibitor SOCS3 in macrophages, inhibition of IL-6 signal transduction by LPS occurs rapidly and does not dependent on gene transcription. Pretreatment of macrophages with IL-10 inhibits subsequent STAT3 activation by IL-6 whereas IL-10-induced STAT3 activation is not affected by preincubation with IL-6. This cross-inhibition is dependent on active transcription and might therefore be explained by different sensitivities of IL-10 and IL-6 signaling towards the feedback inhibitor SOCS3 that is induced by both cytokines. Whereas the IL-6 signal transducer gp130 has been previously shown to recruit SOCS3 to one of its phosphotyrosine residues (Y759), sequence comparison of phosphotyrosine motifs suggests that the SH2-domain of SOCS3 does not interact with phosphorylated tyrosine motifs of the IL-10R. Taken together, different sensitivities of IL-10 and IL-6 signaling towards mechanisms that inhibit the Jak/STAT pathway define an important mechanism that contributes to the different anti-inflammatory potencies of these two cytokines.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2002

Author dc:creator

• Niemand, Claudia

Contributors dc:contributor

• Heinrich, P. C.

• info:eu-repo/classification/ddc/610
• Medizin

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-121015%22

OAI identifier oai:identifier

oai:publications.rwth-aachen.de:59208