Interleukin 10 (IL-10)-mediated inhibition of inflammatory cytokine production by human alveolar macrophages

Citation
B. Raychaudhuri et al., Interleukin 10 (IL-10)-mediated inhibition of inflammatory cytokine production by human alveolar macrophages, CYTOKINE, 12(9), 2000, pp. 1348-1355
Citations number
32
Categorie Soggetti
Cell & Developmental Biology
Journal title
CYTOKINE
ISSN journal
10434666 → ACNP
Volume
12
Issue
9
Year of publication
2000
Pages
1348 - 1355
Database
ISI
SICI code
1043-4666(200009)12:9<1348:I1(IOI>2.0.ZU;2-V
Abstract
Alveolar macrophages are an important source of inflammatory cytokines in t he lung. IL-10 has been shown to inhibit inflammatory cytokine production b y human alveolar macrophages, but mechanisms are unclear. The purpose of th e present study was to investigate whether IL-10 modified cytokine producti on by interference with transcriptional pathways. Alveolar macrophages were obtained from healthy controls by fiberoptic bronchoscopy and incubated wi th LPS +/- IL-10. Results indicated that steady state mRNA levels of tumour necrosis factor-alpha (TNF) and interleukin 1-beta (IL-1) decreased in the presence of IL-10. Consequently, electrophoretic mobility shift assays wer e performed using end-labelled nuclear factor-kappa B (NF-kappa B) or activ ator protein-1 (AP-1) probe. NF-kappa B binding was decreased in extracts f rom macrophages incubated for 4 h with LPS+IL-10 in comparison to those inc ubated with LPS alone. IL-10 also inhibited TNF secretion and NF-kappa B ac tivation induced by another stimulus, staphylococcal toxin, Supershift assa ys revealed the presence of both p50 and p65 subunits of NF-kappa B. AP-1 w as not affected by IL-10. Further examination of mechanisms indicated that IL-10 delayed the LPS-mediated degradation of the inhibitor protein I kappa B, thus delaying the nuclear translocation of the p65 subunit, These obser vations provide the first evidence that IL-10 antagonizes cytokine transcri ption in human alveolar macrophages by impeding the nuclear translocation o f NF-kappa B by delaying the degradation of I kappa B. (C) 2000 Academic Pr ess.