Epithelial cells represent an important source of cytokines that may modulate the influx and functions of mononuclear phagocytes. The aim of our study was to characterize changes in the gene expression of selected cytokines in human macrophages co-cultured with respiratory epithelial cells. The A549 alveolar type II-like cell line was co-cultured with THP-1 cells (monocyte/macrophage cell line) in filter-separated mode to avoid their cell-cell contact. At different time-points (0, 4, 8, 12 and 24 h), the cells were harvested separately to evaluate their gene and protein expression (IL-1 beta, IL-6, IL-8, IL-10 and GM-CSF). Quantitative RT-PCR analysis showed prominent changes in the THP-1 cytokine gene expression induced by a co-culture with A549 cells. Fourfold upregulation of mRNA expression has been found in 12 genes and 4-fold downregulation in 5 genes as compared to the unstimulated control sample with a p value smaller than 0.05. The induction of inhibin beta A and IL-1 beta mRNA after 12 h and the expression of IL-1 alpha and GM-CSF mRNA after 24 h were the most prominent. When looking at the cytokine levels in culture supernatants, IL-1 beta and IL-8 were induced early (at 8 h) as compared to the release of IL-6 and GM-CSF (at 24 h). We conclude that respiratory epithelial cells constitutively regulate the cytokine gene expression of macrophages located in their environment and might further modulate the release of cytokines by posttranslational pathways.

Department of Immunogenetics Institute for Clinical and Experimental Medicine Videnska 1958 9 Prague Czech Republic

Zobrazit více v PubMed

Immunol Lett. 2000 Mar 1;71(3):185-90 PubMed

J Immunol. 2002 Jun 1;168(11):5477-82 PubMed

Am J Respir Crit Care Med. 2000 Apr;161(4 Pt 1):1349-54 PubMed

Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5592-6 PubMed

Biochem Biophys Res Commun. 1987 Feb 13;142(3):1095-103 PubMed

Immunity. 1999 Feb;10(2):137-42 PubMed

Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4560-5 PubMed

J Exp Med. 1992 Nov 1;176(5):1387-98 PubMed

Exp Hematol. 1992 Nov;20(10):1235-42 PubMed

Nat Rev Immunol. 2010 Feb;10(2):89-102 PubMed

J Exp Med. 1992 Nov 1;176(5):1449-52 PubMed

J Leukoc Biol. 1994 Feb;55(2):280-8 PubMed

Cancer Res. 2001 Oct 1;61(19):7240-7 PubMed

Nat Rev Immunol. 2003 Jan;3(1):23-35 PubMed

Trends Immunol. 2002 Aug;23(8):403-8 PubMed

J Immunol. 2000 Jun 15;164(12):6166-73 PubMed

Inflammation. 2001 Aug;25(4):241-6 PubMed

Nat Rev Immunol. 2005 Dec;5(12):953-64 PubMed

The Role of Alveolar Epithelial Type II-Like Cells in Uptake of Structurally Different Antigens and in Polarisation of Local Immune Responses